Clinicopathologic and molecular features of pancreatic adenocarcinoma associated with Peutz-Jeghers syndrome

Cancer Biology and Therapy

Volumn 2, Issue 1, 2003, Pages 39-48

  Yee, Nelson S ^a   Furth, Emma E ^a   Pack, Michael ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Colorectal cancer; Oncogene; Pancreatic cancer; Peutz Jeghers syndrome; Serine threonine kinase; STK11 LKB1; Tumor suppressor; Zebrafish

Indexed keywords

PROTEIN SERINE THREONINE KINASE; STK11 PROTEIN, HUMAN; STK11 PROTEIN, MOUSE;

ADENOCARCINOMA; AGED; CASE REPORT; COLON TUMOR; FEMALE; GENETICS; HUMAN; LYMPH NODE METASTASIS; METASTASIS; MOLECULAR BIOLOGY; PANCREAS TUMOR; PATHOLOGY; PEUTZ JEGHERS SYNDROME; REVIEW;

ADENOCARCINOMA; AGED; COLONIC NEOPLASMS; FEMALE; HUMANS; LYMPHATIC METASTASIS; MOLECULAR BIOLOGY; PANCREATIC NEOPLASMS; PEUTZ-JEGHERS SYNDROME; PROTEIN-SERINE-THREONINE KINASES;

EID: 0038498340     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.191     Document Type: Article

References (137)

1. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin 2002; 52:23-47.
2. Lima CMSR, Centeno B. Update on pancreatic cancer. Curr Opin Oncol 2002; 14:424-30. (Pubitemid 34747979)
3. Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer. 2002; 2:897-909. (Pubitemid 37328891)
4. Bardeesy N, Sharpless NE, DePinho RA, Merlino G. The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model. Seminars in Cancer Biology 2001; 11:201-18. (Pubitemid 32619863)
5. Lynch HT, Brand RE, Deters CA, Shaw TG, Lynch JF. Hereditary pancreatic cancer. Pancreatology 2001; 1:466-71. (Pubitemid 33681749)
6. Hemminki A, Tomlinson I, Markie D, Jarvinen H, Sistonen P, Bjorkqvist A-M, et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nature Genet 1997; 15:87-90. (Pubitemid 27014956)
7. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998; 391:184-7. (Pubitemid 28092478)
8. Jenne DE, Reimann H, Nezu J-I, Friedel W, Loff S, Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998; 18:38-43. (Pubitemid 28027876)
9. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000; 119:1447-53. (Pubitemid 32198669)
10. Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, et al. Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 1999; 154:1835-40. (Pubitemid 29262866)
11. Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, et al. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 2001; 159:2017-22. (Pubitemid 33104257)
12. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. N Engl J Med 1993; 328:1433-7. (Pubitemid 23143844)
13. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich C, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996; 14:141-5. (Pubitemid 26338792)
14. Lowenfels AB, Maisonneuve P, Whitcomb DC. Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group. Med Clin North Am 2000; 84:565-73. (Pubitemid 30346152)
15. Tersmette AC, Petersen GM, Offerhaus GJA, Falatko FC, Brune KA, Goggins M, et al. Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 2001; 7:738-44. (Pubitemid 32708001)
16. Eberle MA, Pfutzer R, Pogue-Geile KL, Bronner MP, Crispin D, Kimmey MB, et al. A new susceptibility locus for autosomal dominant pancreatic cancer maps to chromosome 4q32-34. Am J Hum Genet 2002; 70:1044-8. (Pubitemid 34259323)
17. Lynch HT, Fusaro RM. Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome. Pancreas 1991; 6:127-31.
18. Goldstein AM, Fraser MC, Struewing JP, Hussussian CJ, Ranade K, Zametkin DP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med 1995; 333:970-4.
19. Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, et al. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 1994; 8:27-31.
20. Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 1997; 57:3126-30. (Pubitemid 27351723)
21. Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 1994; 265:2088-90. (Pubitemid 24325690)
22. Tulinius H, Olafsdottir GH, Sigvaldason GH, Tryggvadottir L, Bjarnadottir K. Neoplastic diseases in families of breast cancer patients. J Med Genet 1994; 31:618-21. (Pubitemid 24241408)
23. Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 1996; 56:5360-4. (Pubitemid 27011364)
24. Lynch HT, Smyrk T, Kern SE, Hruban RH, Lightdale CJ, Lemon SJ, et al. Familial pancreatic cancer: A review. Sem Oncol 1996; 23:251-75. (Pubitemid 26120245)
25. Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, et al. Identification of FAP locus gene from chromosome 5q21. Science 1991; 253:661-5. (Pubitemid 21917199)
26. Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991; 66:589-600.
27. Giardiello FM, Offerhaus GJA, Lee DH, Krush AJ, Tersmette AC, Booker SV, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 1993; 34:1394-6. (Pubitemid 23293626)
28. Horii A, Nakatsuru S, Miyoshi Y, Ichii S, Nagase H, Ando H, et al. Frequent somatic mutations of the APC gene in human pancreatic cancer. Cancer Res 1992; 52:6696-8.
29. Yashima K, Nakamori S, Murakami Y, Yamaguchi A, Hayashi K, Ishikawa O, et al. Mutations of the adenomatous polyposis coli gene in the mutation cluster region: Comparison of human pancreatic and colorectal cancers. Int J Cancer 1994; 59:43-7. (Pubitemid 24310946)
30. Lynch HT, Voorhees GJ, Lanspa SJ, McGreevy PS, Lynch JF. Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. Br J Cancer 1985; 52:271-3. (Pubitemid 15229364)
31. Jacob S, Praz F. DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie 2002; 84:27-47. (Pubitemid 34477091)
32. Goggins M, Offerhaus GJ, Hilgers W, Griffin CA, Shekher M, Tang D, et al. Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. Poor differentiation, a syncytial growth pattern, and pushing borders suggest RER+. Am J Pathol 1998; 152:1501-7. (Pubitemid 28275008)
33. Swift M, Sholman L, Perry M, Chase C. Malignant neoplasms in the families of patients with ataxia-telangiectasia. Cancer Res 1976; 36:209-15.
34. Lindor NM, Greene MH. The concise handbook of family cancer syndromes. Mayo Familial Cancer Program. J Natl Cancer Inst 1998; 90:1039-71. (Pubitemid 28350271)
35. Peutz JL. On a very remarkable case of familial polyposis of the mucous membrane of the intestinal tract and nasopharynx accompanied by peculiar pigmentation of the skin and mucous membrane. Ned Tijdschr Geneeskd 1921; 10:134-16.
36. Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits: a syndrome of diagnostic significance. N Engl J Med 1949; 241:992-1005.
37. Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJA, Gittelsohn AM, Booker SV, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987; 316:1511-4. (Pubitemid 17076235)
38. Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, et al. Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 1998; 128:896-99. (Pubitemid 28289483)
39. Thatcher BS, May ES, Taxier MS, Bonta JA, Murthy L. Pancreatic adenocarcinoma in a patient with Peutz-Jeghers syndrome - A case report and literature review. Am J Gastroenterol 1986; 81:594-7. (Pubitemid 16097231)
40. Bowlby LS. Pancreatic adenocarcinoma in an adolescent male with Peutz-Jeghers syndrome. Human Pathology 1986; 17:97-9. (Pubitemid 16163553)
41. Hirao S, Sho M, Kanehiro H, Hisanaga M, Ikeda N, Tsurui H, et al. Pancreatic adenocarcinoma in a patient with Peutz-Jeghers syndrome: Report of a case and literature review. Hepato-Gastroenterology 2000; 47:1159-61.
42. Konishi F, Wyse NE, Muto T, Sawada T, Morioka Y, Sugimura H, et al. Peutz-Jeghers polyposis associated with carcinoma of the digestive organs. Report of three cases and review of the literature. Dis Colon Rectum 1987; 30:790-9.
43. Hizawa K, Iida M, Matsumoto T, Kohrogi N, Kinoshita H, Yap T, et al. Cancer in Peutz-Jeghers syndrome. Cancer 1993; 72:2777-81. (Pubitemid 23320246)
44. Pauwels M, Delcenserie R, Yzet T, Duchmann JC, Capron JP. Pancreatic cystadenocarcinoma in Peutz-Jeghers syndrome. J Clin Gastroenterol 1997; 25:485-92.
45. Yoshikawa A, Kuramoto S, Mimura T, Kobayashi K, Shimoyama S, Yasuda H, et al. Peutz-Jeghers syndrome manifesting complete intussusception of the appendix and associated with a focal cancer of the duodenum and a cystadenocarcinoma of the pancreas. Report of a case. Dis Colon Rectum 1998; 41:517-21. (Pubitemid 28169679)
46. Hruban RH, Canto MI, Yeo CJ. Prevention of pancreatic cancer and strategies for management of familial pancreatic cancer. Dig Dis 2001; 19:76-84. (Pubitemid 32506995)
47. Bolwell JS, James PD. Peutz-Jeghers syndrome with pseudoinvasion of hamartomatous polyps and multiple epithelial neoplasms. Histopathology 1979; 3:39-50. (Pubitemid 9232919)
48. Spigelman AD, Murday V, Phillips RKS. Cancer and the Peutz-Jeghers syndrome. Gut 1989; 30:1588-90. (Pubitemid 20001163)
49. Sohn TA, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 2001; 234:313-22. (Pubitemid 32847068)
50. Sidransky D. Emerging molecular markers of cancer. Nat Rev Cancer 2002; 3:210-9. (Pubitemid 37328790)
51. Fernandez-del Castillo C, Warshaw AL. Cystic neoplasms of the pancreas. Pancreatology 2001; 1:641-7. (Pubitemid 33674961)
52. Cubilla AL, Fitzgerald PJ. Classification of pancreatic cancer (non-endocrine). Mayo Clinic Proc 1979; 54:449-58.
53. Cubilla AL, Fitzgerald PJ. Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Research 1976; 36:2690-8.
54. Hruban RH, Wilentz RE, Goggins M, Offerhaus GJA, Yeo CJ, Kern SE. Pathology of incipient pancreatic cancer. Ann Oncol 1999; 19:S9-11.
55. Meszoely IM, Means AL, Scoggins CR, Leach SD. Developmental aspects of early pancreatic cancer. Cancer J 2001; 7:242-50.
56. Saltz LB, Minsky B. Adjuvant therapy of cancers of the colon and rectum. Surg Clin North Am 2002; 82:1035-58. (Pubitemid 35463083)
57. Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 1997; 225:621-36.
58. McGinn CJ, Lawrence TS, Zalupski MM. On the development of gemcitabine-based chemoradiotherapy regimens in pancreatic cancer. Cancer 2002; 95:393-340.
59. Jaffe EM, Hruban RH, Canto M, Kern SE. Focus on pancreas cancer. Cancer Cell 2002; 2:25-8. (Pubitemid 41043985)
60. Mehenni H, Blouin JL, Radhakrishna U, Bhardwaj SS, Bhardwaj K, Dixit VB, et al. Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4. Am J Hum Genet 1997; 61:1327-34. (Pubitemid 28046909)
61. Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, et al. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet 1998; 63:1641-50. (Pubitemid 30415726)
62. Markie D, Huson S, Maher E, Davies A, Tomlinson I, Bodmer WF. A pericentric inversion of chromosome six in a patient with Peutz-Jeghers' syndrome and the use of FISH to localize the breakpoints on a genetic map. Hum Genet 1996; 98:125-8. (Pubitemid 26237487)
63. Tomlinson IP, Olschwang S, Abelovitch D, Nakiamura Y, Bodmer WF, Thomas G, et al. Testing candidate loci on chromosomes 1 and 6 for genetic linkage to Peutz-Jeghers' disease. Ann Hum Genet 1996; 60:377-84. (Pubitemid 26383909)
64. Wang ZJ, Churchman M, Avizienyte E, McKeown C, Davies S, Evans DG, et al. Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients. J Med Genet 1999; 36:365-8. (Pubitemid 29221870)
65. Boardman LA, Couch FJ, Burgart LJ, Schwartz D, Berry R, McDonnell SK, et al. Genetic heterogeneity in Peutz-Jeghers syndrome. Hum Mutat 2000; 16:23-30. (Pubitemid 30447964)
66. Olschwang S, Boisson C, Thomas G. Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. J Med Genet 2001; 38:356-60. (Pubitemid 32554303)
67. Scott RJ, Crooks R, Meldrum CJ, Thomas L, Smith CJA, Mowat D, et al. Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients. Clin Genet 2002; 62:282-7. (Pubitemid 36372743)
68. Buchet-Poyau K, Mehenni H, Radhakrishna U, Antonarakis SE. Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2. Cytogenet Genome Res 2002; 97:171-8. (Pubitemid 37485356)
69. Resta N, Stella A, Susca FC, Di Giacomo M, Forleo G, Miccolis I, et al. Two novel mutations and a new STK11/LKB1 gene isoform in Peutz-Jeghers patients. Hum Mutat 2002; 20:1-6.
70. Resta N, Simone C, Mareni C, Montera M, Gentile M, Susca F, et al. STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer. Cancer Res 1998; 58:4799-4801. (Pubitemid 28503671)
71. Gruber SB, Entius MM, Petersen GM, Laken SJ, Longo PA, Boyer R, et al. Pathogenesis of adenocarcinoma in Peutz-Jeghers Syndrome. Cancer Res 1998; 58:5267-70. (Pubitemid 28551096)
72. Ylikorkala A, Avizienyte E, Tomlinson IPM, Tiainen M, Roth S, Loukola A, et al. Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer. Hum Mol Genet 1999; 8:45-51. (Pubitemid 29039047)
73. Entius MM, Keller JJ, Westerman AM, van Rees BP, van Velthuysen MLF, de Goeij AFPM, et al. Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome. J Clin Pathol 2001; 54:126-31. (Pubitemid 32128414)
74. Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S, Trink B, Engles JM, et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res 2002; 62:3659-62. (Pubitemid 34728843)
75. Avizienyte E, Roth S, Loukola A, Hemminki A, Lothe RA, Stewig AE, et al. Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors. Cancer Res 1998; 58:2087-90. (Pubitemid 28232890)
76. Dong SM, Kim KM, Kim SY, Shin MS, Na EY, Lee SH, et al. Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer. Cancer Res 1998; 58:3787-90. (Pubitemid 28405631)
77. Park WS, Moon YW, Yang YM, Kim YS, Kim YD, Fuller BG, et al. Mutations of the STK11 gene in sporadic gastric carcinoma. Int J Oncol 1998; 13:601-4. (Pubitemid 28372688)
78. Bignell GR, Barfoot R, Seal S, Collins N, Warren W, Stratton M. Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in sporadic breast cancer. Cancer Res 1998; 58:1384-7.
79. Avizienyte E, Loukola A, Roth S, Hemminki A, Tarkkanen M, Salovaara R, et al. LKB1 somatic mutations in sporadic tumors. Am J Pathol 1999; 154:677-81. (Pubitemid 29122586)
80. Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS. Intraductal papillary-mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer 2002; 94:62-77. (Pubitemid 34049043)
81. Jiang C-Y, Esufali S, Berk T, Gallinger S, Cohen Z, Tobi M, et al. STK11/LKB1 germline mutations are not identified in most Peutz-Jeghers syndrome patients. Clin Genet 1999; 56:136-41. (Pubitemid 29433595)
82. Olschwang S, Markie D, Seal S, Neale K, Phillips R, Cottrell S, et al. Peutz-Jeghers disease most, but not all, families are compatible with linkage to 19p13.3. J Med Genet 1998; 35:42-4. (Pubitemid 28156490)
83. Sato N, Ueki T, Fukushima N, Iacobusio-Donahue CA, Yeo CJ, Cameron JL, et al. Aberrant methylation of CpG islands in intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology 2002; 123:365-72. (Pubitemid 34747556)
84. Fukushima N, Sato N, Ueki T, Rosty C, Walter KM, Wilentz RE, et al. Aberrant methylation of preproenkephalin and p16 genes in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. Am J Pathol 2002; 160:1573-81. (Pubitemid 34525637)
85. Jansen M, Fukushima N, Rosty C, Walter K, Altink R, Heek TV, et al. Aberrant methylation of the 5′ CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanlNs. Cancer Biol Ther 2002; 1:293-6.
86. Esteller M, Avizienyte E, Corn PG, Lothe RA, Baylin SB, Aaltonen LA, et al. Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene 2000; 19:164-8. (Pubitemid 30066364)
87. Almoguerra C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988; 53:549-54.
88. Hruban RH, van Mansfeld AD, Offerhaus GJ, van Weering DH, Allison DC, Goodman SN, et al. K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol 1993; 143:545-54. (Pubitemid 24058210)
89. Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, et al. p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymers tract in DNA microdeletions. Cancer Res 1994; 54:3025-33. (Pubitemid 24187791)
90. Hahn SA, Schutte M, Hoque ATMS, Moskaluk CA, da Costa LT, Rozenblum E, et al. DPC4, a candidate tumor suppressor gene at 18q21.1. Science 1996; 271:350-3.
91. Tascilar M, Offerhaus GJ, Altink R, Argani P, Sohn TA, Yeo CJ, et al. Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct. Am J Clin Pathol 2001; 116:831-7. (Pubitemid 33108153)
92. Smith DP, Spicer J, Smith A, Swift S, Ashworth A. The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase. Hum Mol Genet 1999; 8:1479-85. (Pubitemid 29374081)
93. Kemphues KJ, Priess JR, Morton DG, Cheng NS. Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 1988; 52:311-20.
94. Su JY, Erikson E, Maller JL. Cloning and characterization of a novel serine/ threonine protein kinase expressed in early Xenopus embryos. J Biol Chem 1996; 271:14430-7. (Pubitemid 26190342)
95. Collins SP, Reoma JL, Gamm DM, Uhler MD. LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo. Biochem J 2000; 345 Pt 3:673-80. (Pubitemid 30099098)
96. Rowan A, Churchman M, Jefferey R, Hanby A, Poulsom R, Tomlinson I. In situ analysis of LKB1/STK11 mRNA expression in human normal tissues and tumours. J Pathol 2000; 192:203-6.
97. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, et al. The Peutz-Jeghers gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell 2001; 7:1307-19. (Pubitemid 32607363)
98. Luukko K, Ylikorkala A, Tiainen M, Makela TP. Expression of LKB1 and PTEN tumor suppressor genes during mouse embryonic development. Mech Dev 1999; 83:187-90. (Pubitemid 29302094)
99. Smith A, Ashworth A. Cancer predisposition: where's the phosphate? Curr Bio 1998; 8:241-3.
100. Watts JL, Morton DG, Bestman J, Kemphues KJ. The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry. Development 2000; 127:1467-75. (Pubitemid 30232597)
101. Ylikorkala A, Rossi DJ, Korsisaari N, Luukko K, Alitalo K, Henkemeyer M, et al. Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science 2001; 293:1323-6. (Pubitemid 32777423)
102. Jishage K-I, Nezu J-I, Kawase Y, Iwata T, Watanabe M, Miyoshi A, et al. Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in embryogenesis and polyposis. Proc Natl Acad Sci USA 2002; 99:8903-8. (Pubitemid 34693656)
103. Bardeesy N, Sinha M, Hezel AF, Signoretti S, Hathaway NA, Sharpless NE, et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 2002; 419:162-7. (Pubitemid 35025443)
104. Miyoshi H, Nakau M, Ishikawa TO, Seldin MF, Oshima M, Taketo MM. Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Cancer Res 2002; 62:2261-6. (Pubitemid 34411702)
105. Rossi DJ, Ylikorkala A, Korsisaari N, Salovaara R, Luukko K, Launonen V, et al. Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis. Proc Natl Acad Sci USA 2002; 99:12327-32.
106. Nakau M, Miyoshi H, Seldin MF, Imamura M, Oshima M, Taketo MM. Hepatocellular carcinoma caused by loss of heterozygosity in Lkb1 gene knockout mice. Cancer Res 2002; 62:4549-53.
107. Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer 2001; 1:157-162. (Pubitemid 33741891)
108. Haffter P, Granato M, Brand M, Mullins MC, Hammerschmidt M, Kane DA, et al. The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 1996; 123:1-36. (Pubitemid 27056733)
109. Driever W, Solnica-Krezel L, Schier A F, Neuhauss SCF, Malicki J, Stemple DL, et al. A genetic screen for mutations affecting embryogenesis in zebrafish. Development 1996; 123:37-46. (Pubitemid 27056734)
110. Golling G, Amsterdam A, Sun Z, Antonelli M, Maldonado E, Chen W, et al. Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nat Genet 2002; 31:135-40.
111. Nasevicius A, Ekker SC. Effective targeted gene 'knockdown' in zebrafish. Nat Genet 2000; 26:216-20.
112. Pack M, Solnica-Krezel L, Malicki J, Neuhauss SCF, Schier AF, Stemple DL, et al. Mutations affecting development of zebrafish digestive organs. Development 1996; 123:321-8. (Pubitemid 27056759)
113. Yee NS, Pack M. Zebrafish as a model for pancreatic cancer research. Methods Mol Med 2003; in press.
114. Wallace KN, Pack M. Unique and conserved aspects of gut development in zebrafish. Dev Biol 2003; in press.
115. Roy S, Qiao T, Wolff C, Ingham PW. Hedgehog signaling pathway is essential for pancreas specification in the zebrafish embryo. Curr Biol 2001; 1358-63. (Pubitemid 32835877)
116. diIorio PJ, Moss JB, Sbrogna JL, Karlstrom RO, Moss LG. Sonic hedgehog is required early in pancreatic islet development. Dev Biol 2002; 244:75-84.
117. Yee NS, Yusuff S, Pack M. Zebrafish pdx1 morphant displays defects in pancreas development and digestive organ chirality, and potentially identifies a multipotent pancreas progenitor cell. Genesis 2001; 30:137-40. (Pubitemid 32730759)
118. Huang H, Liu N, Lin S. Pdx-1 knockdown reduces insulin promoter activity in zebrafish. Genesis 2001; 30:134-6. (Pubitemid 32730758)
119. Yoo LI, Chung DC, Yuan J. LKB1 - A master tumour suppressor of the small intestine and beyond. Nat Rev Cancer 2002; 2:529-35. (Pubitemid 37328934)
120. Tiainen M, Ylikorkala A, Makela TP. Growth suppression by Lkb1 is mediated by a G1 cell cycle arrest. Proc Natl Acad Sci USA. 1999; 96:9248-51. (Pubitemid 29374740)
121. Sapkota GP, Kieloch A, Lizcano JM, Lain S, Arthur JS, Williams MR, et al. Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth. J Biol Chem 2001; 276:19469-82.
122. Sapkota GP, Boudeau J, Deak M, Kieloch A, Morrice N, Alessi DR. Identification and characterization of four novel phosphorylation sites (Ser431, Ser325, Thr336 and Thr366) on LKB1/STK11, the protein kinase mutated in Peutz-Jeghers cancer syndrome. Biochem J 2002; 362:481-90. (Pubitemid 34214492)
123. Sapkota GP, Deak M, Kieloch A, Morrice N, Goodarzi AA, Smythe C, et al. Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366. Biochem J 2002; 368:507-16. (Pubitemid 35454528)
124. Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP. Growth arrest by the LKB1 tumor suppressor: induction of p21WAF1/CIP1. Hum Mol Genet 2002; 11:1497-504. (Pubitemid 34679250)
125. Smith DP, Rayter SI, Niederlander C, Spicer J, Jones CM, Ashworth A. LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. Hum Mol Genet 2001; 10:2869-77. (Pubitemid 34030918)
126. Marignani P, Kanai F, Carpenter CL. LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest. J Biol Chem 2001; 276:32415-8.
127. Nezu J, Oku A, Shimane M. Loss of cytoplasmic retention ability of mutant LKB1 found in Peutz-Jeghers syndrome patients. Biochem Biophys Res Commun 1999; 261:750-5. (Pubitemid 29408129)
128. Wilentz RE, Iacobuzio-Donahue CA, Argani P, McCarthy DM, Parsons JL, Yeo CJ, et al. Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res 2000; 60:2002-6. (Pubitemid 30207663)
129. Malumbres M, Pellicer A. RAS pathways to cell cycle control and cell transformation. Front Biosci 1998; 3:d887-912.
130. Gazdar AF, Butel JS, Carbone M. SV40 and human tumours: myth, association or casualty? Nat Rev Cancer 2002; 2:957-64.
131. Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, et al. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell 1994; 77:829-39. (Pubitemid 24187681)
132. Serrano M, Lee H-W, Chin L, Cordon-Cardo C, Beach D, DePinho RA. Role of the INK4a locus in tumor suppression and cell mortality. Cell 1996; 85:27-37. (Pubitemid 26116804)
133. Serrano M, Lin AW, McCurrach ME, Beach, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997; 88:593-602. (Pubitemid 27152402)
134. Steinbach G, Lynch PM, Phillips RKS, Wallace MH, Hawk E, Gordon GB, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000; 342:1946-52. (Pubitemid 30419089)
135. Gupta RA, DuBois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001; 1:11-21. (Pubitemid 33741877)
136. Grosser T, Yusuff S, Cheskis E, Pack MA, Fitzgerald GA. Developmental expression of functional cyclooxygenases in zebrafish. Proc Natl Acad Sci USA 2002; 99:8418-23. (Pubitemid 34651067)
137. Amatruda JF, Shepard JL, Stern HM, Zon, LI. Zebrafish as a cancer model system. Cancer Cell 2002; 1:229-31. (Pubitemid 41039146)