Field cancerization, clonality, and epithelial stem cells: The spread of mutated clones in epithelial sheets

Journal of Pathology

Volumn 187, Issue 1, 1999, Pages 61-81

  Garcia, Sergio Britto ^a   Park, Hyun Sook ^a   Novelli, Marco ^a,b   Wright, Nicholas A ^a,c  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^c IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

Clonality; Crypt fission; Field cancerization; Mutated clones; Stem cells; Tumours

Indexed keywords

CARCINOGENESIS; CLONE; CLONOGENESIS; CRYPT CELL; HAMARTOMA; PHENOTYPE; PRIORITY JOURNAL; REVIEW; STEM CELL;

EID: 0345130005     PISSN: 00223417     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1096-9896(199901)187:1<61::AID-PATH247>3.0.CO;2-I     Document Type: Review

References (287)

1. Shibata D. The dynamics of early intestinal tumour proliferation: to be or not to be. Cancer Surv 1998; 32: 181-200.
2. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996; 87: 159-170.
3. Kinzler KW, Vogelstein B. Gatekeepers and caretakers. Nature (London) 1997; 386: 761-763.
4. Kim SH, Roth KA, Moser AR, Gordon JI. Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia. J Cell Biol 1993; 123: 877-893.
5. Chung GT, Sunderasan V, Hasleton P, Rudd R, Taylor R, Rabbitts P. Sequential molecular changes in lung cancer development. Oncogene 1995; 11: 2591-2598.
6. Tahara E. Molecular biology of gastric cancer. World J Surg 1995; 19: 484-490.
7. Ponten F, Berg C, Ahmadian A. Molecular pathology in basal cell cancer with p53 as a genetic marker. Oncogene 1997; 15: 1059-1067.
8. Wainscoat JS, Fey MF. Assessment of clonality in human tumours: a review. Cancer Res 1990; 50: 1355-1360.
9. Fukayama M, Hayashi Y, Iwasaki Y, et al. Epstein-Barr virus-associated gastric carcinoma and Epstein Barr virus infection of the stomach. Lab Invest 1994; 71: 73-81.
10. MaClain KL, Leach CTR, Jenson HB, et al. Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS. N Engl J Med 1995; 332: 12-18.
11. Leung SY, Chung LP, Yuen ST, Wong MP, Chan SY. Lymphoepithelial carcinoma of the salivary gland: in situ detection of Epstein Barr virus. J Clin Pathol 1995; 48: 1022-1027.
12. Raab-Traub N, Flynn K. The structure of the termini of the Epstein Barr virus as a marker of clonal cellular proliferation. Cell 1986; 47: 883-889.
13. Jiang X, Yao KT. The clonal progression in the neoplastic process of nasopharyngeal carcinoma. Biochem Biophys Res Commun 1996; 2212: 122-128.
14. Hsu HC, Chiou TJ, Chen JY, Lee CS, Lee PH, Peng SY. Clonality and clonal evolution of hepatocellular carcinoma with multiple nodules. Hepatology 1991; 13: 923-928.
15. Fialkow PJ Clonal origin of tumours. Biochim Biophys Acta 1976; 458: 283-321.
16. Vogelstein B, Fearon ER, Hamilton SR, Feinberg AP. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumours. Science 1985; 227: 624-645.
17. Sternlicht M, Mirell C, Safarians S, Barsky S. A novel strategy for the investigation of clonality in precancerous disease states and early stages of tumor progression. Biochem Biophys Res Commun 1994; 199: 511-518.
18. Fraser NJ, Boyd Y, Craig I. Isolation and characterisation of a human variable copy number tandem repeat at Xeen-p11.22. Genomics 1989; 5: 144-148.
19. Abrahamson G, Fraser NJ, Boyd Y, Craig I, Wainscoat JC. A highly informative X-chromosome probe M27β can be used for the determination of clonality. Br J Haematol 1990; 14: 371-377.
20. Liu Y, Phelan J, Go RCP, Prchal J, Prchal J. Rapid determination of clonality by detection of two closely-linked X chromosome exonic polymorphisms using allele-specific PCR. J Clin Invest 1997; 99: 1984-1990.
21. Lyon MF. X-chromosome inactivation and developmental patterns in mammals. Biol Rev 1972; 47: 1-35.
22. Jones PA. DNA methylation errors and cancer. Cancer Res 1996; 56: 2463-2467.
23. Silva AJ, Ward K, White R. Mosaic methylation in clonal tissue. Dev Biol 1993; 156: 391-398.
24. Cedar H. DNA methylation and gene activity. Cell 1988; 53: 3-4.
25. Vogelstein B, Fearon ER, Hamilton SR, et al. Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res 1987; 47: 4806-4813.
26. Fey MF, Peter HJ, Hinds HL. Clonal analysis of human tumours with M27β, a highly informative polymorphic X-chromosome probe. J Clin Invest 1992; 89: 1438-1444.
27. Jones PA, Buckley JD. The role of DNA methylation in cancer. Adv Canter Res 1990; 54: 1-23.
28. Jacobs IJ, Kohler MF, Wiseman RW, et al. Clonal origin of epithelial ovarian carcinoma; analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation. J Nat Cancer Inst 1992; 84: 1793-1798.
29. Wilimas JA, Dow LW, Douglass, EC, et al. Evidence for clonal development of Wilms' tumour. Am J Pediatr Oncol 1991; 13: 26-28.
30. Drya PT, Mukai S, Petersen R, Rappaport JM, Walton D, Yandell DW. Paternal origin of mutation in the retinoblastoma gene. Nature 1989; 339: 556-558.
31. Yun K. Genomic imprinting and carcinogenesis. Histol Histopathol 1998; 13: 425-435.
32. Tiny F, Vogt N, Recan D, et al. Skewed inactivation of an X chromosome deleted at the dystrophin gene in an asymptomatic mother and her affected daughter. Hum Genet 1994; 93: 563-567.
33. Wengler GS, Allen RC, Parolini O, Smith H, Conley ME. Non-random X-chromosome inactivation in natural killer cells from obligate carriers of X-linked severe combined immunodeficiency. J Immunol 1993; 150: 700-704.
34. Mutter G, Boynton K. PCR bias in amplification of androgen receptor alleles, a trinucleotide repeat marker used in clonality studies. Nucleic Acid Res 1995; 23: 1411-1418.
35. Gale RE, Wheadon H, Linch DC. Assessment of X-chromosome inactivation patterns using the hypervariable probe M27β in normal hemopoietic cells and acute myeloid leukaemia blasts. Leukemia 1992; 6: 649-655.
36. Boyd Y, Fraser NJ. Methylation patterns of the hypervariable X-chromosome locus DXS255 (M27β): correlation with X-inactivation status. Genomics 1990; 7: 182-187.
37. Lo Coco F, Pelicci PG, D'Adamo F. Polyclonal hemopoietic reconstitution in leukemia patients at remission after suppression of specific gene rearrangements. Blood 1982; 82: 606-612.
38. Lo Coco F, D'Adamo F, Diverio D, Pelicci PG, Saglio G. Polyclonal haemopoiesis in leukaemia patients following molecularly documented remission. Leukaemia 1994; 8(Suppl 1): S137-S139.
39. Fialkow P. Primordial cell pool size and lineage relationships of five human cell types. Ann Hum Genet 1973; 37: 39-48.
40. Tate JE, Mutter GL, Boynton KA, Crum CT. Monoclonal origin of vulvar intraepithelial neoplasia and some vulvar hyperplasias. Am J Pathol 1997; 150: 315-322.
41. Thomas GA, Williams D, Williams ED. The demonstration of tissue clonality by X-linked enzyme histochemistry. J Pathol 1988; 155: 101-108.
42. Tan S, Williams E, Tam P. X-inactivation occurs at different times in different tissues of the post-implantation mouse embryo. Nature Genet 1993; 3: 170-174.
43. Dijhuizen SMMM, Entius MM, Clement MJ, et al. Multiple hyperplastic polyps in the stomach: evidence for clonality and neoplastic potential. Gastroenterology 1997; 112: 561-566.
44. Franklin WA, Gazdar AF, Haney J, et al. Widely dispersed p53 mutation in respiratory epithelium. J Clin Invest 1997; 100: 2133-2137.
45. Ozturk M p53 mutations in hepatocellular carcinoma after aflatoxin exposure. Lancet 1991; 338: 1356-1359.
46. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 1991; 350: 427-428.
47. Lasky T, Magder L. Hepatocellular carcinoma p53 G → T transversions at codon 249: the fingerprint of aflatoxin exposure? Environ Health Perspect 1997; 105: 392-397.
48. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253: 49-53.
49. Lee CC, Liu YY, Lin LK, Chu JS, Shew JY. p53 point mutations enhanced by hepatic regeneration in aflatoxin B1-induced rat liver tumors and preneoplastic lesions. Cancer Lett 1998; 125: 1-7.
50. Fey MF, Wells RA, Wainscoat JS. Assessment of clonality in gastrointestinal cancer by DNA fingerprinting. J Clin Invest 1988; 82: 1532-1537.
51. Nakashima H, Honda M, Inoue H, et al. Microsatellite instability in multiple gastric cancers. Int J Pathol 1995; 64: 239-242.
52. Shinmura K, Tani M, Isogaki J, Wang Y, Sugimara H, Yokota J. RER phenotype and its associated mutations in familial gastric cancer. Carcinogenesis 1998; 19: 247-251.
53. Panagoulos I, Pandis N, Thelin S, et al. The FHIT and PTRG genes are deleted in benign proliferate breast disease associated with familial breast cancer and cytogenetic rearrangements of chromosome hand 3p14. Cancer Res 1996; 56: 4871-4875.
54. Dietrich CU, Pandis N, Teixeira MR, Bardi G, Gerdes A-M, Andersen J. Chromosome abnormalities in benign hyperproliferative disorders of epithelial and stromal breast tissue. Int J Cancer 1995; 60: 49-53.
55. Larson PS, Morenas A, Cupples LA, Huang K, Rosenberg CL. Genetically abnormal clones in histologically normal breast tissue. Am J Pathol 1998; 152: 1591-1598.
56. Teixeira MR, Pandis N, Bardi G, Andersen JA, Mitelman F, Heim S. Clonal heterogeneity in breast cancer: karyotypic comparisons of multiple intra- and extra-tumorous samples from 3 patients. Int J Cancer 1995; 63: 63-68.
57. Schmidt GH, Mead R. On the clonal origin of tumours - lessons from studies of intestinal epithelium . BioEssays 1990; 12: 37-40.
58. Woodruff MFA. Tumour clonality: biological significance. Adv Cancer Res 1988; 50: 197-229.
59. Walsh DS, Peacocke M, Harrington A, James WD, Tsou HC. Patterns of X-chromosome inactivation in sporadic basal cell carcinomas: evidence for clonalily. J Am Acad Dermatol 1998; 38: 49-55.
60. Farber E. Monoclonal and polyclonal development of digestive tract tumors in chimeric mice. Jpn J Cancer Res 1997; 88: 245.
61. Sawada M, Azuma C, Hashimoto K, et al. Clonal analysis of human gynecologic cancers by means of the polymerase chain reaction. Int J Cancer 1994; 58: 492-496.
62. Niho S, Suzuki K, Yokose T, Kodama T, Nishiwaka Y, Esumi H. Monoclonality of both pale cells and cuboidal cells of sclerosing hemangioma of the lung. Am J Pathol 1998; 152: 1065-1069.
63. Kawai S, Imazeki F, Yokosuka O, et al. Clonality in hepatocellular carcinoma: analysis of methylation pattern of polymorphic X-chromosome-linked phosphoglycerate kinase gene in females. Hepatology 1995; 22: 112-117.
64. Barsky SH, Grossman DA, Ho J, Holmes EC. The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin. Mod Pathol 1994; 7: 633-640.
65. Apel RL, Ezzat S, Bapat B, Pan N, LiVolsi VA, Asa S. Clonality of thyroid nodules in sporadic goitre. Diagn Mol Pathol 1995; 4: 113-121.
66. Chung I-M, Schwartz SM, Murry CE. Clonal architecture of normal and atherosclerotic aorta. Implications for atherogenesis and vascular development. Am J Pathol 1998; 152: 913-923.
67. Benditt EP, Benditt JM. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Nat Acad Sciences USA 1973; 70: 1753-1756.
68. Murry CE, Gipaya CT, Bartosek T, Benditt EP, Schwartz SM. Monoclonality of smooth muscle cells in human atherosclerosis. Am J Pathol 1997; 151: 697-706.
69. Lemire JM, Covin CW, White C, Giachelli CM, Schwartz SM. Characterisation of cloned aortic smooth muscle cells from young rats. Am J Pathol 1994; 144: 1068-1081.
70. Schwartz SM, Murry CE. Proliferation and the monoclonal origins of atherosclerotic lesions. Ann Rev Med 1998; 49: 437-460.
71. Iannaccone PM. Clone and patch size in chimaeric mouse skin. Math Biosc 1980; 51: 117-123.
72. Shroyer KR, Gudlaugsson EG. Analysis of clonality in archival tissues by polymerase chain reaction amplification. Hum Pathol 1925; 25: 287-292.
73. Williams GT, Wynford Thomas D. How may clonality be studied in human tumours?. Histopathology 1994; 24: 287-292.
74. Fey MF, Tobler A. Tumour heterogeneity and clonality an old theme revisited. Ann Oncol 1996; 7: 121-128.
75. Piao Z, Park YN, Kim H, Park C. Clonality of large regenerative nodules in liver cirrhosis. Liver 1997; 17: 251-256.
76. Enomoto T, Haba T, Fujita M, et al. Clonal analysis of high-grade squamous intraepithelial lesions of the uterine cervix. Int J Cancer 1997; 73: 339-344.
77. Krohn K, Fuhrer D, Holzappel HP, Paschke R. Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations. J Clin Endocrinol Metab 1998; 83: 130-134.
78. Noguchi S, Motomura K, Inaji H, Imoaka S, Koyama H. Clonal analysis of human breast cancer by means of the polymerase chain reaction. Cancer Res 1992; 52: 6594-6597.
79. Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 194: 23-28.
80. Woodruff MFA, Ansell JD, Forbes SM, Gordon J, Burton D, Micklem HS. Clonal interaction in tumours. Nature 1982; 299: 822-831.
81. Winton DJ, Blount MA, Ponder BAJ. Polyclonal origin of mouse skin papillomas. Br J Cancer 1989; 60: 59-63.
82. Teixeira MR, Pandis N, Bardi G, et al. Cytogenetic analysis of multifocal breast carcinomas: detection of karyotypically unrelated clones as well as clonal similarities between tumour foci. Br J Cancer 1994; 70: 922-927.
83. Heim S, Caron M, Jin Y, Mandahl N, Mitelman F. Genetic convergence during serial in vitro passage of a polyclonal squamous carcinoma. Cytogenet Cell Genet 1989; 52: 133-135.
84. Shibata D, Schaeffer J, Li Z, Capella G, Perucho M. Genetic heterogeneity of the c-K-ras locus in colorectal adenomas but not in adenocarcinoma. J Nat Cancer Inst 1993; 85: 1058-1063.
85. Sidransky D, Frost P, von Eschenbach A, Oyasu R, Preisinger AC, Vogelstein B. Clonal origin of bladder cancer. N Engl J Med 1992; 326: 737-740.
86. Iannaconne PM, Weinberg WC, Deamant FD. On the clonal origin of tumours: a review of experimental models. Int J Cancer 1987; 39: 778-784.
87. Novelli MR, Williamson JA, Tomlinson IPM, et al. Polyclonal origin of colonie adenomas in an XO/XY patient with FAP. Science 1996; 272: 1187-1190.
88. Nomura S., Kaminishi M, Sugiyama K, Oohara T, Esumi H. Clonal analysis of isolated single fundic and pyloric glands of stomach using X-linked polymorphisms. Biochem Biophys Res Commun 1996; 226: 385-390.
89. Nesbitt M, X-Chimaeras v. X-inactivation mosaics: significance of pigment distribution. Dev Biol 1974; 38: 202-207.
90. West JD. Clonal development of the retinal epithelium in mouse chimaeras and X-inactivation mosaics. J Embryol Exp Morphol 1976; 35: 445-446.
91. West JD. Patches in livers of chimaeric mice. J Embryol Exp Morphol 1976; 36: 151-161.
92. Weinberg WC, Howard JC, Iannaconne PM. Histological demonstration of mosaicism in a series of chimeric rats produced between congenic strains. Science 1985; 227: 524-527.
93. Khocka MK, Landini G, Iannacconne PM. Fractal geometry in rat chimaeras demonstrates that a repetitive cell division program may generate liver parenchyma. Dev Biol 1994; 165: 545-555.
94. Zajicek G, Owen R, Weinreb M. The streaming liver. Liver 1985; 5: 293-300.
95. Ng Y-K, Iannoccone PM. Fractal geometry of mosaic pattern demonstrates that liver regeneration is a self-similar process. Dev Biol 1992; 151: 419-430.
96. Bralet M-P, Brancherau S, Brechot C, Ferry N. Cell lineage study in the liver using retroviral-mediated gene transfer. Am J Pathol 1994; 144: 896-905.
97. Kennedy S, Rettinger S, Flye MW, Ponder KP. Experiments on transgenic mice show that hepatocyles are the source for postnatal liver growth and do not stream. Hepatology 1995; 22: 160-168.
98. Deamant RD, Iannoconne PM. Clonal origin of chemically-induced papillomas: separate analysis of epidermis and dermal components. J Cell Sci 1987; 88: 305-314.
99. Gartler SM, Gandini E, Hutchinson HT, Campbell B, Zechhi G. Glucose-6-phosphate dehydrogenase mosaicism: utilisation of the study of hair follicles. Ann Hum Genet 1971; 35: 1-7.
100. Schmidt GH, Blount MA, Ponder BAJ. Immunochemical demonstration of the clonal organisation of chimaeric mouse epidermis. Development 1987; 100: 535-541.
101. Tsai YC, Lu Y, Nichols PW. Contiguous patches of normal human mammary epithelium derived from a single stem cell: implications for breast carcinogenesis. Cancer Res 1996; 56: 402-404.
102. Deng G, Lu Y, Zlotnikov G, Thor AD, Smith HS. Loss of heterozygosity in normal tissue adjacent to breast carcinoma. Science 1996; 274: 2057-2059.
103. Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development 1998; 125: 1921-1940.
104. Tsai YC, Simoneau AR, Spruck CH, Nicholas PW, Steven K, Jones PA. Mosaicism in human epithelium: macroscopic mosaic patches cover the urothelium. J Urol 1995; 153: 1697-1700.
105. Linder G, Gartler SM. Distribution of glucose-6-phosphate dehydrogenase electrophoretic variants in different tissues of heterozygotes. Am J Hum Genet 1965; 45: 212-220.
106. Linder G, Gartler SM. Glucose-6-phosphate dehydrogenase mosaicism: utilisation as a cell marker for the study of leiomyomas. Science 1965; 150: 67-69.
107. Deerlin PGV, Cekleniak N, Coutifaris C, Boyd J, Strauss JF. Evidence for the oligoclonal origin of the granulosa cell population of the mature human follicle. J Clin Endocrinol Metab 1997; 82: 3019-3024.
108. Thompson EM, Fleming KA, Evans DJ, Fundele R, Surani MA, Wright NA. Gastric endocrine cells share a clonal origin with other gut cell lineages. Development 1990; 110: 477-481.
109. Pearse AGE. Clonality and endocrine (APUD) cell tumours. In: Polak JM, Bloom SL, eds. Endocrine Tumours. Edinburgh: Churchill Livingstone, 1981; 82-94.
110. Ponder BAJ, Schmidt GH, Wilkinson MM, Wood MJ, Monk M, Reid A. Derivation of mouse intestinal crypts from single progenitor cells. Nature 1987; 127: 381-391.
111. Schmidt GH, Winton DJ, Ponder BAJ. Development of the pattern of cell renewal in the crypt-villus unit of the mouse small intestine. Development 1988; 103: 785-790.
112. Griffiths DFR, Davies SJ, Williams D, Williams GT, Williams ED. Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry. Nature 1988; 333: 461-463.
113. Winton D, Blount MA, Ponder BA. A clonal marker induced by mutation in mouse intestinal epithelium. Nature 1988; 333: 463-466.
114. Wright NA. Stem cell repertoire in the intestine. In: Potten CS, ed. Stem Cells. New York: Academic Press, 1996; 315-327.
115. Tatematsu M, Masui T, Fukami H, et al. Primary monoclonal and secondary polyclonal growth of colon neoplastic lesions in C3H/BeN↔BALB/c chimeric mice treated with 1,2-dimethylhydrazine: immunohistochemical detection of C3H strain-specific antigen and simple sequence polymorphism analysis of DNA. Int J Cancer 1996; 66: 234-238.
116. Williams ED, Lowes AP, Williams D, Williams GT. A stem cell niche theory of intestinal crypt maintenance based on a study of somatic mutation in colonie mucosa. Am J Pathol 1993; 141: 773-776.
117. Park H-S, Goodlad RA, Wright NA. Crypt fission in the small intestine and colon: a mechanism for the emergence of glucose-6-phosphate locus-mutated crypts after mutagen treatment. Am J Pathol 1995; 147: 1416-1427.
118. Campbell F, Williams GT, Appleton MAC, Dixon MF, Harris M, Williams ED. Post-irradiation somatic mutation and clonal stabilisation time in the human colon. Gut 1996; 39: 569-573.
119. Loeffler M, Birke A, Winton D, Pollen CS. Somatic mutation, monoclonality and stochastic models of stem cell organisation in the intestinal crypt. J Theor Biol 1993; 160: 471-491.
120. Loeffler M, Bratke T, Paulus U, Li YQ, Poten CS. Clonalily and life cycles of intestinal crypts explained by a state dependent stochastic model of epithelial stem cell organisation. J Theor Biol 1997; 186: 41-54.
121. Fuller CE, Davies RP, Williams GT, Williams ED. Crypt restricted heterogeneity of goblet cell mucus glycoprotein in histologically-normal colonie mucosa: a potential marker of somatic mutation. Br J Cancer 1990; 61: 382-384.
122. Campbell F, Fuller CH, Williams GT, Williams ED. Human colonic stem cell mutation frequency with and without irradiation. J Pathol 1994; 174: 175-182.
123. Williams GT, Geraghty JM, Campbell F, Appleton MAC, Williams ED. Normal colonie mucosa in hereditary non-polyposis colorectal cancer shows no generalised increase in somatic mutation. Br J Cancer 1995; 71: 1077-1080.
124. Campbell F, Appleton M, Shields CJ, Williams GT. No difference in stem cell somatic mutation between the background mucosa of right and left-sided sporadic coloreclal carcinomas. J Pathol 1998; 186: 31-35.
125. Endo Y, Sugimara H, Kino I. Monoclonality of normal human colonic crypts. Pathol Int 1995; 45: 602-604.
126. Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 1990; 110: 1001-1020.
127. Hendry JH, Roberts SA, Potten CS. The clonagen content of murine intestinal crypts: dependence on radiation dose used in ils determination. Radiat Res 1992; 132: 115-119.
128. Jiang X, Hitchcock A, Bryan EJ, et al. Microsatellite analysis of endoetriosis reveals loss of heterozygosity at candidate ovarian tumour suppressor gene loci. Cancer Res 1996; 56: 3534-3539.
129. Pearson TA, Solez K, Dillman J, Heptinstall R. Monoclonal characteristics of organising arterial thrombi: significance in the origin and growth of human atherosclerotic plaques. Lancet 1979; 1: 7-11.
130. Pearson TA, Dillman JM, Solez K, Heptinstall RH. Clonal markers in the study of the origin and growth of human atherosclerotic lesions. Circ Res 1978; 43: 10-18.
131. Pearson TA, Dillman JM, Heptinstall RH. Clonal mapping of the human aorta: relationship of monoclonal characteristics, lesion thickness, and age in normal intima and atherosclerotic lesions. Am J Pathol 1987; 126: 33-39.
132. Casalone R, Granata P, Minelli E, et al. Cytogenetic analysis reveals clonal proliferation of smooth muscle cells in atherosclerotic lesions. Hum Genet 1991; 87: 139-143.
133. MaCaffrey TA, Du B, Consigli S, et al. Genomic instability in the type II TGFβ1 receptor gene in atherosclerotic and restenotic vascular cells. J Clin Invest 1997; 100: 2182-2188.
134. Slaughter DP, Southwick HW, Smejkal W. 'Field cancerisation' in oral stratified squamous epithelium. Cancer 1953; 6: 963-968.
135. Chung GTY, Sundaresan V, Hasleton P, Rudd R, Taylor R, Rabbitts PH. Sequential molecular genetic changes in lung cancer development. Oncogene 1995; 11: 2591-2598.
136. Yang HK, Linnola RI, Conrad NK, et al. TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract. Int J Cancer 1995; 64: 229-233.
137. Gusterson BA, Anbazhagan R, Warren W, et al. Expression of p53 in premalignant and malignant squamous epithelium. Oncogene 1991; 6: 1785-1789.
138. Worsham MJ, Wolam SR, Carey TF, Zarbo RJ, Benninger MS, Van Dyke DL. Common clonal origin of synchronous head and neck squamous cell carcinoma: analysis by tumor karyotypes and fluorescence in situ hybridisation. Hum Pathol 1995; 26: 251-261.
139. Sozzi G, Miozzo M, Pastorino U, et al. Genetic evidence for an independent origin of multiple preneoplastic and neoplastic lung lesions. Cancer Res 1995; 55: 135-140.
140. Kang GH, Kim CJ, Kim WH, Kang YK, Kim HO, Kim YI. Genetic evidence for the multicentric origin of synchronous gastric carcinoma. Lab Invest 1997; 76: 407-417.
141. Fearon FR, Hamilton SR, Vogelstein B. Clonal analysis of human colorectal tumours. Science 1987; 238: 193-197.
142. Arnold A, Staunton CE, Kim HJG, Gaz RD, Kronenberg HM. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenoma. N Engl J Med 1988; 318: 658-662.
143. Emmert Buch MR, Vocke CD, Pozzatti RO, et al. Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia. Cancer Res 1995; 55: 2959-2962.
144. Cheng L, Song SY, Pretlow TG, et al. Evidence for independent origin of multiple tumours from patients with prostate cancer. J Nat Cancer Inst 1998; 90: 233-237.
145. Dumont P, Gasser B, Rouge C, Massard G, Wihlm JM. Bronchoalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically-treated patients. Chest 1998; 113: 391-395.
146. Mashal RD, Fezjo MLS, Friedman AJ, et al. Analysis of androgen receptor DNA reveals independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata. Genes Chromosomes Cancer 1994; 11: 11-16.
147. Hashimoto K, Azuma C, Kamiura S, et al. Clonal determination of uterine leioniyomas by analysing differential inactivation of the X-chromosome-linked phosphoglyceraokinase gene. Gynecol Obstet Invest 1995; 40: 204-208.
148. Howell S, Wareham KA, Williams ED. Clonal origin of mouse liver cell tumours. Am J Pathol 1985; 121: 426-432.
149. Tsunoshima K, Endo V, Asakuura H, et al. A novel clonality assay for the mouse: application to hepatocellular carcinomas induced with diethylnitrosoamine. Mol Carcinogen 1996; 15: 33-37.
150. Weinberg WC, Iannoccone PM. Clonality of preneoplastic liver lesions: histological analysis in chimaeric rats. J Cell Svi 1988; 89: 423-431.
151. Tsuda H, Hirohashi S, Shimasato Y, Terada M, Hasegawa H. Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma. Gastroenterology 1988; 95: 1664-1666.
152. Gaffey MJMJ, Iezzoni JC, Weiss JM. Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol 1996; 148: 1089-1096.
153. Sheu J-C. Molecular mechanism of hepatocarcinogenesis. J Gastroenterol Hepatol 1997; 12(Suppl): S309-S313.
154. Esumi M, Aritaka T, Arii M. Clonal origin of human hepatoma determined by integration of hepatitis B virus DNA. Cancer Res 1986; 46: 5767-5771.
155. Hsumi M, Tanaka Y, Tozuka S, Shikata T. Clonal state of human hepatocellular carcinoma and non-tumorous hepatocytes. Cancer Chemother Pharmacol 1989; 23(Suppl): 1-3.
156. Govindarajan S, Craig JR, Valinluck B. Clonal origin of hepatitis B-associated hepatocellular carcinoma. Hum Pathol 1988; 19: 403-405.
157. Chen D-S, Lai M-Y, Chang M-H, et al. Clonal origin of recurrent hepatocellular carcinomas. Gastroenterology 1989; 96: 527-529.
158. Shimoda A, Kaneko S, Uchijama M. Clonal origin of mammalian hepatitis B virus related hepatocellular carcinoma. J Med Virol 1990; 30: 282-286.
159. Lunec J, Challen C, Wright C, Mellon K, Neal D . c-erb2 amplification and identical p53 mutations in concomitant transitional carcinomas of renal pelvis and urinary bladder. Lancet 1992; 339: 439-440.
160. Li S, Han U, Resnik E, Carcangiu ML, Schwartz PE, Yang-Feng TL. Advanced ovarian carcinoma: molecular evidence of unifocal origin. Gynecol Oncol 1993; 51: 21-25.
161. Moh CH, Tsao SW, Knapp RC, Fishbaugh PM, Lau CC. Unifocal origin of advanced human epithelial ovarian cancers. Cancer Res 1992; 52: 5119-5122.
162. Kupryjanezyk J, Beauchamp R, Poremba C, Scully RE, Yandell DW. Ovarian peritoneal and endometrial serous carcinoma: clonal origin of multifocal disease. Mod Pathol 1996; 9: 31-49.
163. Pejovic T, Heim S, Mandahl N, et al. Bilateral ovarian carcinomas: cytogenetic evidence of unicentric origin. Int J Cancer 1991; 47: 358-361.
164. Ahomadegbe JC, Barrois M, Fogel S. High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumours and metastases; absence of correlation with clinical outcome, frequent protein overexpression in normal epithelium and in early non-invasive lesions. Oncogene 1995; 10: 1217-1227.
165. Gallo O, Bianchi S. p53 expression: a potential biomarker for risk of multiple primary malignancies in the upper aerodigestive tract. Eur J Cancer 1995; 31B: 53-57.
166. Nakanishi Y, Noguchi M, Matsuno Y. p53 expression in multicentric squamous cell carcinoma and surrounding squamous epithelium of the upper aerodigestive tract. Cancer 1995; 75: 1657-1662.
167. Brennan JA, Mao I, Hrudan RH. Molecular assessment of histopathological staging in squamous cell carcinoma of the head and neck. N Engl J Med 1995; 332: 429-435.
168. Chung NY, Mukhopahhyay T, Kim J, et al. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res 1993; 53: 1676-1683.
169. Mandard AM, Marnay J, Lebeau C, Banard S, Mandard JC. Expression of p53 in oesophageal epithelium from surgical specimens resected for squamous carcinoma of the oesophagus, with special reference to uninvolved mucosa. J Pathol 1997; 181: 153-157.
170. Ogden GR, Hall PA. Field change, clonality and early epithelial cancer: possible lessons from p53. J Pathol 1997; 181: 127-129.
171. Nees M, Homann D, Discher H. Expression of mutated p53 occurs in tumour-distant epithelium of head and neck cancer patients: a possible molecular basis for the development of multiple tumours. Cancer Res 1993; 53: 4139-4196.
172. Ren Z-P, Ponten F, Nister M, Ponten J. Two distinct p53 immunohistochemical patterns in human squamous skin cancer, precursors and normal epidermis. Int J Cancer 1966; 69: 174-179.
173. Ren Z-P, Ahmadian A, Ponten E. Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin. Am J Pathol 1997; 150: 1791-1803.
174. Ren Z-P, Ponten F, Nister M, Ponten J. Reconstruction of the two-dimensional distribution of p53 positive staining patches in sun-exposed, morphologically-normal skin. Int J Oncol 1997; 1: 111-115.
175. Jonasson AS, Kunala S, Price GJ. Frequent clones of p53-mutated keratinocytes in normal skin. Proc Natl Acad Sci USA 1996; 93: 14025-14029.
176. Heinen CD, Noffsinger AE, Belli J, et al. Regenerative lesions in ulcerative colitis are characterised by microsatellite mutation. Genes Chromosomes Cancer 1997; 19: 170-175.
177. Brentall TA, Crispin DA, Bronner MP, et al. Microsatellite instability in non-neoplastic mucosa from patients with chronic ulcerative colitis. Cancer Res 1996; 56: 1237-1240.
178. Sunderasan V, Ganly P, Hasleton P, et al. p53 and chromosome 3 abnormalities characteristic of malignant lung tumours are detectable in preinvasive lesions of the bronchus. Oncogene 1991; 7: 1989-1997.
179. Dolcetti R, Doglioni C, Maestro R, et al. p53 overexpression is an early event in the development of human squamous cell carcinoma of the larynx - genetic and prognostic implications. Int J Cancer Res 1992; 52: 178-182.
180. Sameshima Y, Matsumo Y, Hirohashi S, et al. Alterations of the p53 gene are common and critical events for the maintenance of the malignant phenotypes in small cell lung carcinoma. Oncogene 1992; 7: 451-457.
181. Boyle JO, Hakim J, Koch W. The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Res 1993; 53: 4477-4480.
182. Rabkin CS, Bedi G, Musaba E. AIDS-related Kaposi's sarcoma is a monoclonal neoplasm. Clin Cancer Res 1995; 1: 257-260.
183. Rabkin CS, Janz S, Lash A. Monoclonal origin of multicentric Kaposi's sarcoma lesions. N Engl J Med 1997; 336: 988-993.
184. Delabresse E, Oksenhendler E, Lebbe C, Verola O, Varel B, Turhan AG. Molecular analysis of clonality in Kaposi's sarcoma. J Clin Pathol 1997; 50: 654-668.
185. Gill P, Tsai Y, Rao AP, Jones P. Clonality in Kaposi's sarcoma. N Engl J Med 1997; 8: 571-572.
186. Kattar MM, Kupsky WJ, Shimoyama RK, et al. Clonal analysis of gliomas. Hum Pathol 1997; 28: 1166-1179.
187. Stangl AP, Wellenreuther R, Lenartz D, et al. Clonality of multiple meningiomas. J Neurosurg 1997; 86: 853-858.
188. Zhu J, Frosch M, Busque L, et al. Analysis of meningiomas by methylation and transcription-based clonality assays. Cancer Res 1995; 55: 3865-3872.
189. Jimbo H, Hitomi Y, Yoshikawa H, et al. Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts. Am J Pathol 1997; 150: 1173-1178.
190. Nilbert M, Pejovic T, Mandahl N, Iosif S, Willen H, Mitelman F. Monoclonal origin of endometriotic cysts. Int Gynecol Cancer 1995; 5: 61-63
191. Tamura M, Fukaya T, Murakami T, Uehara S, Yajima A. Analysis of clonality in human endometriotic cysts based on evaluation of X-chromosotne inactivation in archival formalin-fixed, paraffin-embedded tissue. Lab Invest 1988; 78: 213-218.
192. Fox H. Pathology of early malignant change in the ovary. Int J Gynecol Pathol 1993; 12: 153-155.
193. Tavassoli F, Kraus F. Endometrial lesions in uteri resected for atypical endometrial hyperplasia. Am J Clin Pathol 1978; 70: 770-779.
194. Esteller M, Garcia A, Martinez-Palonesa JM, Xercavins J, Reventos J. Detection of clonality and genetic alterations in endometrial pipelle biopsy and its surgical specimen counterpart. Lab Invest 1997; 76: 109-116.
195. Hicks DG, LiVolsi VA, Neidich JA, Puck JM, Kant JA. Clonal analysis of solitary follicular nodules in the thyroid. Am J Pathol 1990; 137: 553-562.
196. Thomas GA, Williams D, Williams ED. The clonal origin of thyroid nodules and adenomas. Am J Pathol 1989; 134: 141-147.
197. Namba H, Matsuo K, Fagin JA. Clonal composition of benign and malignant human thyroid tumours. J Clin Invest 1990; 86: 120-125.
198. Apel RL, Ezzat S, Bapat BV, Pan N, LiVolsi VA, Asa SL. Clonality of thyroid nodules in sporadic goitre. Diagn Mol Pathol 1995; 4: 113-121.
199. Aeschimann S, Kopp PA, Kimura ET, et al. Morphological and functional polymorphism within clonal thyroid nodules. J Clin Endocrinol Metab 1993; 77: 846-851.
200. Namba H, Ross JL, Goodman D, Fagin JA. Solitary polyclonal autonomous thyroid nodule: a rare cause of childhood hyperthyroidism. J Clin Endocrinol Metab 1991; 72: 1108-1102.
201. Bamburger AM, Bamburger CM, Barth J, Heidorn K, Kreipe H, Schulte HM. Clonal composition of thyroid nodules from patients with multinodular goiters: determination by X-chromosome inactivation analysis with M27beta. Exp Clin Endocrinol 1993; 49(Suppl 1): 73.
202. Kopp P, Kimura ET, Aeschimann S, et al. Polyclonal and monoclonal thyroid nodules coexist within human multinodular goiters. J Clin Endocrinol 1994; 79: 134-139.
203. Alexander P. Do cancers arise from a single transformed cell or is monoclonality of tumours a late event in carcinogenesis?. Br J Cancer 1985; 51: 453-457.
204. Thomas GA, Williams D, Williams ED. Clonal origin of thyroid tumours. In: Wynford-Thomas D, Williams ED, eds. Thyroid Tumours: Molecular Basis of Pathogenesis. Edinburgh: Churchill Livingstone, 1988; 38-56.
205. Baylin SB, Gann DS, Hsu SH. Clonal origin of inherited medullary carcinoma and phaeochromocytoma. Science 1976; 193: 321-322.
206. Baylin SB, Hsu HS, Gann DS, Smallridge RC, Wells SA. Inherited medullary carcinoma: a final monoclonal mutation in one of multiple clones of susceptible cells. Science 1978; 199: 429-431.
207. Ferraris AM, Mangerini R, Gaetani GF, Romei C, Pinchera A, Pacini F. Polyclonal origin of medullary carcinoma of the thyroid in multiple endocrine neoplasia type 2. Hum Genet 1997; 99: 202-205.
208. Fialkow Jackson CE, Block MA, Greenawald KA. Multicellular origin of parathyroid 'adenomas'. N Engl J Med 1977; 297: 696-698.
209. Jackson CE, Cerny JC, Block MAS, Fialkow PJ. Probable clonal origin of aldosteronomas versus multicellular origin of parathyroid 'adenomas'. Surgery 1982; 92: 875-879.
210. Arnold A, Staunton C, Kim HG, Randall AB, Gaz D, Kronenberg HM. Monoclonality and abnormal parathyroid genes in parathyroid adenomas. N Engl J Med 1988; 318: 658-662.
211. Noguchi S, Motomura K, Inaji H, Imoaka S, Koyama H. Clonal analysis of parathyroid adenomas by means of the polymerase chain reaction. Canter Lett 1997; 78: 93-97.
212. Friedman E, Sakaguchi K, Bale AE, et al. Clonality of parathyroid tumours in familial multiple endocrine neoplasia type 1. N Engl J Med 1989; 321: 213-218.
213. Lubensky IA, Debelenko LV, Zhuang Z, et al. Allelic deletions on chromosome 11q13 in multiple tumours from individual MEN1 patients. Cancer Res 1996; 56: 5272-5278.
214. Arnold A, Brown MF, Urena P, Gaz RD, Sarfati E, Drueke TB. Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. J Clin Invest 1995; 95: 2047-2053.
215. Falchetti A, Bale LE, Amorosi C, et al. Progression of uraemic hyperparathyroidism involves allelic loss on chromosome 11. J Clin Endocrinol Metab 1993; 76: 139-144.
216. Shan L, Nalamura M, Nakamura V, et al. Comparative analysis of clonality and pathology in primary and secondary hyperparathyroidism. Virckows Arch 1997; 430: 247-251
217. Tominaga T, Kohara S, Namil Y, et al. Clonal analysis of nodular parathyroid hyperplasia in renal hyperparathyroidism. World J Surg 1996; 20: 744-752.
218. Harada M, Suzuki M, Ikeda T, Kaneko T, Harad S, Fukayama M. Clonality in nevocellular nevus and melanoma: an expression-based clonality analysis at the X-linked genes by polymerase chain reaction. J Invest Dermatol 1997; 109: 656-660.
219. Green AJ, Sepp T, Yates JRW. Clonality of tuberous sclerosis hamartomas shown by non-random X-chromosome inactivation. Hum Genet 1996; 97: 240-243.
220. Fletcher JA, Pinkus GS, Weidner N, Morton CC. Lineage-restricted clonality in biphasic solid tumours. Am J Pathol 1991; 138: 1199-1207.
221. Park TW, Richart RM, Sun X-W, Wright TC. Association between human papillomavirus type and clonal status of cervical intraepithelial lesions. J Nat Cancer Inst 1996; 88: 355-358.
222. Kim Y-T, Thomas NF, Kessis TD, Wilkinson EJ, Hedrick L, Cho KR. p53 mutations and clonality in vulvar carcinoma and squamous hyperplasias: evidence suggesting that squamous hyperplasias do not serve as direct precursors of human papillomavirus-negative vulvar carcinomas. Hum Pathol 1996; 27: 389-395.
223. Sheu LF, Chen A, Tseng HH, et al. The assessment of p53 expression in nasopharyngeal carcinoma. Hum Pathol 1995; 26: 380-386.
224. Lu QL, Elia G, Thomas JA. Bcl-2 proto-oncogene expression in Epstein Barr virus associated nasopharyngeal carcinoma. Cancer 1993; 53: 29-35.
225. Dawson PJ. What is new in our understanding of multifocal breast cancer? Pathol Res Pract 1993; 189: 111-116.
226. Pandis N, Teiziera MR, Gerdes A-M, et al. Chromosome abnormalities in bilateral breast carcinomas. Cytogenetic evaluation of the clonal origin of multiple primary tumours. Cancer 1995; 76: 250-259.
227. Noguchi S, Motomura K, Inaji H, Imoaka S, Koyama H. Clonal analysis of fibroadenoma and phyllodes tumor of the breast. Cancer Res 1993; 53: 4071-4074.
228. Lu J, Jiang C, Mitrenga T, Cutter G, Thompson HJ. Pathogenetic characterisation of 1-methyl-1-nitrososurea-induced mamman carcinomas in the rat. Carcinogenesis 1998; 19: 223-227.
229. Noguchi S, Aihara T, Koyama H. Discrimination between multicentric and multifocal carcinomas of the breast through clonal analysis. Cancer 1994; 74: 872877.
230. Lakhani SR, Collins N, Stratton MR, Sloane JP. Atypical ductal hyperplasia of the breast: clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p. J Clin Pathol 1995; 48: 611-615.
231. Lakhani SR, Slack DN, Hamoudi RA, Collins N, Stratton MR, Sloane JP. Detection of allelic imbalance indicates that a proportion of mammary hyperplasias of usual type are clonal neoplastic proliferations. Lab Invest 1996; 74: 129-135.
232. Petersson C, Johansson B, Pandis N, Gorunova L, Ingvar C, Idvall I. Clonal chromosome aberrations in fibrocystic disease associated with increased risk of cancer. Int J Oncol 1994; 5: 1207-1210.
233. Chuaquai RF, Zhuang Z, Emmert-Buck MR, Liotta L, Merino M. Analysis of loss of heterozygosity on chromosome 11q13 in atypical duct hyperplasia and in situ carcinoma of the breast. Am J Pathol 1997; 150: 297-303.
234. Kasami M, Vnencak-Jones CL, Manning S, Dupont WD, Page DL. Loss of heterozygosity and microsatellite instability in breast hyperplasia: no obligate correlation of these alterations with subsequent malignancy. Am J Pathol 1997; 150: 1925-1932.
235. Dijhuizen SMM, Entius MM, Clement MUJ, et al. Multiple hyperplastic polyps in the stomach: evidence for clonality and neoplastic potential. Gastroenterology 1997; 112: 561-566.
236. Hahuchi T, Takahashi R, Yamada H, Kakehi Y, Sugiyama T, Yoshida O. Metadironous, multifocal development of urothelial cancers by intra-luminal seeding. Lancet 1993; 342: 1087-1088.
237. Slack JM. Homeotic transformations in man: implications for the mechanism of embryonic development and for the organisation of epithelia. J Theor Biol 1985; 114: 463-490.
238. Nomura S, Kaminishi M, Sugiyama K, Oohara T, Esumi E. Clonal analysis of isolated intestinal metaplastic glands of stomach using X-linked polymorphism. Gut 1998; 42: 663-668.
239. Silva S, Filipe MI, Pinho A. Variants of intestinal metaplasia in the evolution of chronic atrophic gastritis and gastric ulcer. A follow-up study. Gut 1990; 31: 1097-2004.
240. Craancn ME, Blok P, Dekker W, et al. Chronology of p53 protein accumulation in gastric carcinogenesis. Gut 1995; 36: 848-852.
241. Miracco C, Spina D, Vindigni C, Filipe MI, Tosi P. Cell proliferation patterns and p53 in gastric dysplasia. Cancer 1995; 62: 149-154.
242. Brito MJ, Williams GT, Thompson H, Kilipe MI. Expression of p53 in early (T1) gastric carcinoma and pre-cancerous adjacent mucosa. Gut 1994; 35: 1697-1700.
243. Joypaul PV, Newman EL, Hopwood D, et al. Expression of p53 protein in normal, dysplastic and malignant gastric mucosa: an immunohistochemical study. J Pathol 1993; 170: 279-283.
244. Rhyu MG, Park WS, Jung YJ, Choi SW, Meltzer SJ. Allelic deletions of MCC/APC and p53 are frequent late events in human gastric carcinogenesis. Gastroenterology 1994; 106: 1584-1588.
245. Sanz-Ortega J, Sanz-Experona J, Caldes T, Gomez de la Concha E, Sobel ME, Merino MJ. LOH at the APC/MCC gene (5Q21) in gastric cancer and pre-neoplastic lesions. Pathol Res Pract 1996; 192: 1206-1210.
246. Tahara E, Yokohazi H, Yasui W. Growth factors in gastric cancer. In: Nishi M, Ichikawa H, Nakajima T, Maruyama K, Tahara E, eds. Gastric Cancer. Tokyo: Springer-Verlag, 1994; 207-217.
247. Ochiai A, Yamanchi Y, Hirohashi S. p53 mutations in the non-neoplastic mucosa of the human stomach showing intestinal metaplasia. Int J Cancer 1996; 69: 28-33.
248. Goniyo Y, Osaki M, Kaibara N, Ho H. Numerical aberration and point mutation of p53 in human gastric intestinal metaplasia and well-differentiated adenocarcinoma: analysis by fluorescence in situ hybridisation (FISH) and PCR-SSCP. Int J Cancer 1996; 66: 594-599.
249. Wright NA, Alison MR. The Biology of Epithelial Cell Populations. Vol 2. Oxford: Clarendon Press, 1984.
250. Eujita S, Hattori T. Cell proliferation, differentiation and migration in the gastric mucosa: a study of the background of carcinogenesis. In: Farber E, Sigano H. eds. Pathophysiology of Carcinogcnesis in Digestive Organs. Baltimore: University Park Press, 1977; 22-31.
251. Zhuang Z, Vortmeyer A, Mark E, Odze R, Emmert-Huck M, Merino M. Barren's esophagus: metaplastic cells with loss of heterozygosity at the APC gene locus are clonal precursors to invasive adenocarcinoma. Cancer Res 1996; 56: 1961-1964.
252. Bodmer WF, Bailey CJ, Bodmer J, et al. Localisation of the gene for familial adenomatous polyposis on chromosome 5. Nature 1987; 128: 614-616.
253. Beutler E, Collins Z, Lowell E, Irwin MD. Value of genetic variants of glucose-6-phosphate dehydrogenase in tracing the origin of malignant tumours. N Engl J Med 1967; 276: 389-391.
254. Hsu SH, Luk GD, Krush AJ, Hamilton SR, Hoover HH. Multiclonal origin of polyps in Gardner syndrome. Science 1983; 221: 951-953.
255. Ponder BAJ, Wilkinson MM. Direct examination of the clonality of carcinogen-induced colonic epithelial dysplasia in chimeric mice. J Nat Cancer Inst 1986; 77: 967-976.
256. Merritt AJ, Gould KA, Dove WF. Polyclonal structure of intestinal adenomas in Apemin/+ mice from all tumor lineages. Proc Nat Acad Sci USA 1997; 94: 13927-13931.
257. Bjerknes M, Cheng H, Kim H, Schnitzler M, Gallinger S. Clonality of dysplastic epithelium in colorectal adenomas from familial adenomatous polyposis patients. Cancer Res 1997; 57: 355-361.
258. de Wind D, Dekker M, van Rossum A, van der Valk M, de Teile H. Mouse models for hereditary non-polyposis colorectal cancer. Cancer Res 1988; 58: 248-255.
259. Jass JR, Stewart SM, Stewart J, Lane MR. Hereditary non-polyposis colorectal cancer morphologies, genes and mutations. Mutation Res 1994; 310: 125-133.
260. Wasan HS, Park H-S, Liu KC, et al. APC in the regulation of intestinal crypt fission. J Pathol 1998; 185: 246-255.
261. Moolgavkar SH, Luebeck EG. Multistage carcinogenesis: population-based model for colon cancer. J Nat Cancer Inst 1992; 84: 610-618.
262. Melville DM, Jass J, Shephard N, Northover J. Dysplasia and deoxyribonucleic acid aneuploidy in the assessment of precancerous changes in chronic ulcerative colitis: observer variation and correlation. Gastroenterology 1988; 95: 688-675.
263. Levin DS, Rabinovich PS, Haggitt RC, et al. Distribution of aneuploid cell populations in ulceralive colitis with dysplasia or cancer. Gastroenterology 1991; 101: 1198-1210.
264. Burner GC, Rabinovitch PS, Haggitt RC. Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of a p53 allele. Gastroenterology 1992; 103: 1602-1611.
265. Hammerberg C, Rubin C, Slezk P, Tribukait B, Ohman U. Flow cytometric DNA analysis as a means for early detection of malignancy in patients with chronic ulcerative colitis. Gut 1984; 5: 905-908.
266. Fozard JB, Quirke P, Dixon MF, Giles JR, Bird CC. DNA aneuploidy in ulceralive colitis. Gut 1986; 27: 1414-1418.
267. Lofberg R, Tribukait B, Ost A, Brostiam O, Reichardt H. Flow cytometric analysis in long-standing ulcerative colitis: a method of prediction of dysplasia and carcinoma development. Gut 1987; 28: 1101-1106.
268. Rubin CE, Haggitt RC, Brentnall TA, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 1992; 103: 1611-1620.
269. Ahnen DJ. Abnormal DNA content as a biomarker of large bowel cancer risk and prognosis. J Cell Biochem 1992; 16G(Suppl): 143-150.
270. Maskens AOP, Dujardin-Loits RM. Kinetics of tissue proliferation in colorectal mucosa during postnatal growth. Cell Tissue Kinetics 1981; 14: 467-475.
271. Cairnie AB, Millen BH. Fission of crypts in the small intestine of the irradiated mouse. Cell Tissue Kinetics 1975; 8: 189-196.
272. Wright NA, Al-Nafussi A. The kinetics of villus cell populations in the mouse small intestine. II. Studies on growth control after death of proliferative cells induced by cytosine arabinoside, with special reference to negative feedback mechanisms. Cell Tissue kinetics 1982; 15: 611-621.
273. Totofurno J, Bjerknes M, Cheng H. The crypt cycle. Crypt and villus production in the adult intestinal epithelium. Biophys J 1987; 52: 279-294.
274. Bjerknes M. A test of the stochastic theory of stem cell differentiation. Biophys J 1986; 49: 1223-1227.
275. Cheng H, McCullough C, Bjerknes M. Effects of 30% intestinal resection on whole population cell kinetics of mouse intestinal epithelium. Anat Rec 1986; 215: 35-41.
276. Park H-S, Goodlad RA, Ahnen DJ, et al. Effects of epidermal growth factor and dimethylhydrazine on crypt size, cell proliferation and crypt fission in the rat colon. Am J Pathol 1997; 151: 1-10.
277. Cheng H, Bjerknes M, Amar J, Gardiner G. Crypt production in normal and diseased human colonie epithelium. Anat Rec 1986; 216: 44-48.
278. Bjerknes M, Cheng H, Hay K, Gallinger S. APC mutation and the crypt cycle in murine and human intestine. Am J Pathol 1997; 150: 833-839.
279. Bjerknes M. The crypt cycle and the asymptotic dynamics of the proportion of differently sized mutant crypt clones in the mouse intestine. Proc R Soc B London, 1995; 260: 1-6.
280. Park H-S, Goodlad RA, Wright NA. The incidence of aberrant crypt foci and colonie carcinoma in dimethylhydrazine-treated rats varies in a site-specific manner and depends on tumour histology. Cancer Res 1997; 57: 4507-4510.
281. Minkin S. Statistical analysis of aberrant crypt assays for colon promotion studies. Biometrics 1994; 50: 279-288.
282. Paulsen JE, Steffensen I-L, Namark E, Alexander J. Scanning electron microscopy of aberrant crypt foci in the rat colon. Carcinogenesis 1994; 35: 2371-2372.
283. Bjerknes M. Expansion of mutant stem cell populations in the human colon. J Theor Biol 1996; 178: 381-385.
284. Roncucci L, Medline A, Bruce WR. Classification of aberrant crypt foci and microadenomas in human colon. Cancer Epidemiol Biomarkers Prevent 1991; 1: 57-60.
285. Roncucci L, Stamp D, Medline A, Cullen JB, Bruce WR. Identification and quantification of aberrant crypt foci and microadenomas in the human colon. Hum Pathol 1991; 22: 287-294.
286. Pretlow TP, Cheyer C, O'Riordan MA. Aberrant crypt foci and colon tumours in F344 rats have similar increases in proliferative activity. Int J Cancer 1994; 56: 599-602.
287. Araki K, Ogata T, Kobayashi M, Yatani R. A morphological study of the histogenesis of human colorectal polyps. Gastroenterology 1995; 109: 1468-1474.