The molecular genetics of pancreatic ductal carcinoma

Minerva Chirurgica

Volumn 57, Issue 5, 2002, Pages 561-574

  Sohn, T A ^a  

^a DEPARTMENT OF PATHOLOGY   (United States)

Author keywords

Oncogenes; Pancreatic ducts; Pancreatic neoplasms, diagnosis; Pancreatic neoplasms, genetics

Indexed keywords

ACTIVIN RECEPTOR 1; APC PROTEIN; BETA CATENIN; BRCA2 PROTEIN; CYCLIN DEPENDENT KINASE 4; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; PROTEIN; PROTEIN KINASE LKB1; PROTEIN P16; PROTEIN P53; PROTEIN TCF 4; RETINOBLASTOMA PROTEIN; SMAD4 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TUMOR MARKER; UNCLASSIFIED DRUG;

ARTICLE; CANCER GROWTH; CANCER INVASION; CANCER MODEL; CANCER MORTALITY; CANCER STAGING; CANCER SURVIVAL; DNA MICROARRAY; GENE AMPLIFICATION; GENE EXPRESSION; GENE MUTATION; IN SITU HYBRIDIZATION; METASTASIS; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; MOLECULAR BIOLOGY; MOLECULAR GENETICS; MULTIDRUG RESISTANCE; ONCOGENE; ONCOGENE K RAS; PANCREAS CARCINOMA; PANCREAS DUCT CARCINOMA; PANCREAS TUMOR; PANCREATIC INTRAEPITHELIAL NEOPLASIA; POLYMERASE CHAIN REACTION; TUMOR SUPPRESSOR GENE; UNITED STATES;

AGED; BASE PAIR MISMATCH; CARCINOMA IN SITU; CARCINOMA, PANCREATIC DUCTAL; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; DNA MUTATIONAL ANALYSIS; DNA REPAIR; DNA, NEOPLASM; GENE EXPRESSION PROFILING; GENES, TUMOR SUPPRESSOR; HUMANS; MIDDLE AGED; NEOPLASM PROTEINS; NEOPLASTIC SYNDROMES, HEREDITARY; ONCOGENES; PANCREATIC NEOPLASMS;

EID: 0036399762     PISSN: 00264733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (93)

1. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer Statistics, 2001. CA Cancer J Clin 2001;51:16-36.
2. Hruban RH, Peterson GM, Ha PK, Kern SE. Genetics of pancreatic cancer: from genes to families. Surg Oncol Clin North Am 1998;7:1-23.
3. Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature 1997;386:623-7.
4. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998;396:643-9.
5. El-Hanry I, Pignatelli M, Lemoine NR. FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma. Int J Cancer 2001;94:652-61.
6. Ellenrieder V, Hendler SF, Ruhland C, Boeck W, Adler G, Gress TM. TGF-β-induced invasiveness of pancreatic cancer cells is mediated by matrix metalloproteinase-2 and the urokinase plasminogen activator system. Int J Cancer 2001;93:204-11.
7. Ebert M, Yokoyama M, Friess H, Kobrin MS, Buchler MW, Korc M. Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer. Int J Cancer 1995;62:529-35.
8. Friess H, Yamanaka Y, Buchler M, Berger HG, Kobrin MS, Baldwin RL et al. Enhanced expression of the type II transforming growth factor β-receptor in human pancreatic cancer cells without alteration of type III receptor expression. Cancer Res 1993;53:2704-7.
9. Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Peterson GM et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 1996;5:5360-4.
10. Su GH, Hilgers W, Shekher M, Tang D, Yeo CJ, Hruban RH et al. Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. Cancer Res 1998;58:2339-42.
11. Ryu B, Jones J, Hollingsworth MA, Hruban RH, Kern SE. Invasion-specific genes in malignancy: serial analysis of gene expression. Comparisons of primary and passaged cancers. Cancer Res 2001;61:1833-8.
12. Ryu B, Jones J, Blades NJ, Parmigiani G, Hollingsworth MA, Hruban RH et al. Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression. Cancer Res. In press 2002.
13. Iacobuzio-Donahue CA, Ryu B, Hruban RH, Kern SE. Exploring the host desmoplastic response to pancreatic carcinoma. Gene expression of stromal and neoplastic cells at the site of primary invasion. Am J Pathol 2002;160:91-9.
14. Argani P, Iacobuzio-Donahue C, Ryu B, Rosty C, Goggins M, Wilentz RE et al. Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression. Clin Cancer Res 2001;7:3862-8.
15. Argani P, Rosty C, Reiter RE, Wilentz RE, Murugesan SR, Leach SD et al. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res 2001;61:4320-4.
16. Wilentz RE, Geradts J, Maynard R, Offerhaus GJA, Gittesohn AM, Booker SV et al. Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res 1998;58:4740-4.
17. Wilentz RE, Iacobuzio-Donahue CA, Argani P, McCarthy DM, Parsons J, Yeo CJ et al. Loss of expression of DPC4 in pancreatic intraepithelial neoplasia (PanIN): evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res 2000;60:2002-6.
18. Hruban RH, Aday NV, Albores-Saavedra J, Compton C, Garrett E, Goodman SE et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 2001;25:579-86.
19. Hruban RH, Wilentz RE, Kern SE. Genetic progression in the pancreatic ducts. Am J Pathol 2000;156:1821-5.
20. 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 homocopolymer tracts in DNA microdeletions. Cancer Res 1994;54:3025-33.
21. Schutte M, Hruban RH, Geradts J, Maynard R, Higers W, Rabindran SK et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinoma. Cancer Res 1997;57:3126-30.
22. Hruban RH, van Mansfield ADM, Offerhaus GJA, van Weering DHJ, 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.
23. Almoguerra C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant K-ras genes. Cell 1998;53:549-54.
24. Wilentz RE, Goggins M, Redston M, Marcus VA, Adsay NV, Sohn TA et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas. Am J Pathol 2000;156:1641-51.
25. 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.
26. Wilentz RE, Chung DH, Sturn PDJ, Musler A, Sohn TA, Offerhaus GJA et al. K-ras mutations in duodenal fluid of patients with pancreas carcinoma. Cancer 1998;82: 96-103.
27. Boadas J, Mora J, Urgell E, Puig P, Roca M, Cusso X et al. Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer. Eur J Gastroenterol Hepatol 2001;13:1153-9.
28. Ha A, Watanabe H, Yamaguchi Y, Ohtsubo K, Wang Y, Motoo Y et al. Usefulness of supernatent of pancreatic juice for genetic analysis of K-ras in diagnosis of pancreatic carcinoma. Pancreas 2001;23(4):356-63.
29. Berthelemy P, Bouisson M, Escorrou J, Vaysse N, Rumeau JL, Pradayrol L. Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer. Ann Intern Med 1995;123:188-91.
30. Caldas C, Hahn SA, Hruban RH, Redston MS, Yeo CJ, Kern SE. Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal mucinous cell hyperplasia. Cancer Res 1994;54:3568-73.
31. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW et al. Constitutive transcriptional activity by β-catenin-Tcf complex in APC -/- colon carcinoma. Science 1997;275:1784-7.
32. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT et al. Identification of c-MYC as a target of the APC pathway. Science 1998;281:1509-12.
33. He TC, Chan TA, Vogelstein B, Kinzler KW. PPARδ is an APC regulated target of non-steroidal antiinflammatory drugs. Cell 1999;99:335-45.
34. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B et al. Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. Science 1997;275:1787-90.
35. Seymour AB, Hruban RH, Redston M, Caldas C, Powell SM, Kinzler KW et al. Allelotype of pancreatic adenocarcinoma. Cancer Res 1994;54:2761-4.
36. McKie Abm Filipe MI, Lemoine NR. Abnormalities affecting the APC and MCC tumour suppressor gene loci on chromosome 5q occur frequently in gastric cancer, but not pancreatic cancer. Int J Cancer 1993;55:598-603.
37. 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.
38. Caca K, Kolligs FT, Ji X, Hayes M, Qian J, Yahanda A et al. β- and γ-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. Cell Growth Differ 1999;10:369-76.
39. Gerdes B, Ramaswamy A, Simon B, Petsch T, Bastian D, Kersting M et al. Analysis of β-catenin gene mutations in pancreatic tumors. Digestion 1999;60:544-8.
40. Abraham SC, Wu TT, Klimstra DS, Finn LS, Lee JH, Yeo CJ et al. Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas: frequent alterations in the APC/β-catenin pathway and chromosome 11p. Am J Pathol 2001;159(5):1619-27.
41. Tanaka Y, Kato K, Notohara K, Hojo H, Ijiri R, Miyake T et al. Frequent β-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm. Cancer Res 2001;61:8401-4.
42. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK et al. Amplification of AKT2 in human pancreatic cancer cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 1996;93:3636-41.
43. Ruggeri BA, Huang L, Wood M, Cheng JQ, Testa JR. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol Carcinog 1998;21:81-6.
44. Wallrapp C, Muller-Pillasch F, Solinas-Toldo S, Lichter P, Friess H, Buchler M et al. Characterization of a high copy number amplification of 6q24 in pancreatic cancer identifies c-myb as a candidate oncogene. Cancer Res 1997;57:3135-9.
45. 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;8:27-32.
46. 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 carcinoma. Cancer Res 1997;57:3126-30.
47. Mosakluk CA, Hruban RH, Kern SE. p16 and K-ras mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res 1997;57:2140-3.
48. INK4 allele (Asp145Cys) in a family with multiple pancreatic carcinomas. Hum Mutat 1998;12(1):70.
49. Lal G, Liu G, Schmocker B, Kaurah P, Ozcelik H, Narod SA et al. Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations. Cancer Res 2000;60: 409-16.
50. Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JJ, Hruban RH. Hypermethylaton of multiple genes in pancreatic adenocarcinoma. Cancer Res 2000;60:1835-9.
51. INK4, p53, MDM2, and Rb. Ann Surg 2002;235: 51-9.
52. Ruggeri B, Zhang SY, Caamano J, DiRado M, Flynn SD, Klein-Szanto AJ. Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes. Oncogene 1992;7:1503-11.
53. Ceha HM, Clement MJ, Polak MM, Offerhaus GJ, Slebos RJ. Mutational analysis of the p16-binding domain of cyclin-dependent kinase 4 in tumors in the head region of the pancreas. Pancreas 1998;17:85-8.
54. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997;88:323-31.
55. Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B. Identification and classification of p53-regulated genes. Proc Natl Acad Sci USA 1999;96: 14517-22.
56. Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S et al. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell 1997;1: 3-11.
57. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E et al. DPC4, a candidate tumor-suppressor gene at human chromosome 18q21.1. Science 1996;271:350-3.
58. Wilentz RE, Su GH, Dai JL, Sparks AB, Argani P, Sohn TA et al. Immunohistochemical labeling for DPC4 mirrors genetic status in pancreatic adenocarcinomas. A new marker for DPC4 inactivation. Am J Pathol 2000;156:37-43.
59. Tascilar M, Offerhaus JG, 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.
60. Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJA et al. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res 2001;7:4115-21.
61. Zawel L, Dai JL, Buckhaults P, Zhou S, Kinzler KW, Vogelstein B et al. Human Smad3 and Smad4 are sequence specific transcription activators. Mol Cell 1998;1:611-7.
62. Dai JL, Turnacioglu K, Schutte M, Sugar AY, Kern SE. Dpc4 transcriptional activation and dysfunction in cancer cells. Cancer Res 1998;58:4592-7.
63. Hanafusa H, Ninomiya-Tsuji J, Masuyama N, Nishita M, Fujisawa J, Shibuya H et al. Involvement to the p38 mitogen-activated protein kinase pathway in transforming growth factor-β-induced gene expression. J Biol Chem 1999;274:27161-7.
64. Engel ME, McDonnell MA, Law BK, Law BK, Moses HL. Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription. J Biol Chem 1999;274:37413-20.
65. Hocevar BA, Brown TL, Howe PH. TGF-β induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO 1999;18:1345-56.
66. Dai JL, Schutte M, Bansal RK, Wilentz RE, Sugar AY, Kern SE. Transforming growth factor-β responsiveness in DPC4/SMAD4-null cancer cells. Mol Carcinog 1999;26:37-43.
67. Sirard C, Kim S, Mirtsos C, Tadich P, Hoodless PA, Itie A et al. Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor-β related signaling. J Biol Chem 2000;275: 2063-70.
68. Baldwin RL, Freiss H, Yokoyama M, Lopez ME, Kobrin MS, Buchler MW et al. Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with resistance to growth inhibition. Int J Cancer 1996;67:283-8.
69. Goggins M, Shekher M, Turnacioglu K, Yeo CJ, Hruban RH, Kern SE. Genetic alterations of the transforming growth factor β receptor genes in pancreatic and biliary adenocarcinomas. Cancer Res 1998;58:5329-32.
70. Lu SL, Kawabata M, Imamura T, Akiyama Y, Nomizu T, Miyazono K et al. HNPCC accociated with germline mutations in the TGF-β type II receptor gene. Nat Genet 1998;19:17-8.
71. Su GH, Bansal R, Murphy KM, Montgomery E, Yeo CJ, Hruban RH et al. ACVR1B (ALK4, activin receptor type IB) gene mutations in pancreatic cancer. Proc Natl Acad Sci USA 2001;98:3254-7.
72. Teng DHF, Perry WL III, Hogan JK, Baumgard M, Bell R, Berry S et al. Human mitogen-activated protein kinase 4 as a candidate tumor suppressor. Cancer Res 1997;57:4177-82.
73. 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;345:673-80.
74. Tiainen M, Ylikorkala A, Makela TP. Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest. Proc Natl Acad Sci USA 1999;96:9248-51.
75. Su GH, Hruban RH, Bansal RK, Bova DS, 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(6):1835-40.
76. Giardello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV et al. Increase risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987;316:1511-4.
77. Goggins M, Hruban RH, Kern SE. BRCA2 is inactivated late in the development of pancreatic intraepithelial neoplasia: evidence and implications. Am J Pathol 2000;156(5):1767-71.
78. Hruban RH, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Falatko F et al. Familial pancreatic cancer. Ann Oncol 1999;10:69-73.
79. Tersmette AC, Petersen GM, Offerhaus GJA, Falatko FC, Brune KA, Goggins MG 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.
80. Hruban RH, Canto MI, Yeo CJ. Prevention of pancreatic cancer and strategies for management of familial pancreatic cancer. Dig Dis 2001;19:76-84.
81. Lynch HT, Brand RE, Lynch JF, Fusaro RM, Smyrk TC, Goggins M et al. Genetic counseling and testing for germline p16 mutations in two pancreatic cancer-prone families. Gastroenterology 2000;119:1756-60.
82. Solcia EM, Capella C, Kloppel G. Atlas of tumor pathology: tumors of the pancreas. Washington, DC: Armed Forces Institute of Pathology; 1997.
83. Balague C, Audie JP, Porchet N, Real FX. In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues. Gastroenterology 1995;109(3):953-64.
84. Shimizu M, Saitoh Y, Ohyanagi H, Itoh H. Immunohistochemical staining of pancreatic cancer with CA199, KM01, unabsorbed CEA, and absorbed CEA. Arch Pathol Lab Med 1990;114:195-200.
85. Terada T, Ohta T, Sasaki M, Nakanuma Y, Kim YS. Expression of MUC apomucins in normal pancreas and pancreatic tumours. J Pathol 1996;180(2):160-5.
86. Ritts RE, Pitt HA. CA 19-9 in pancreatic cancer. Surg Oncol Clin North Am 1998;7:93-101.
87. Iacobuzio-Donahue CA, Hruban RH. Pancreatic ductal adenocarcinoma. In: Ladanyi M, Gerald W, editors. Expression profiling of human tumors. Diagnostic and research applications. Hum Press. In press 2002.
88. Velculescu VE, Zhang L, Vogelstein B, Kinzler KW. Serial analysis of gene expression. Science 1995;270: 484-7.
89. Fernandez Zapico ME, Ahmad US, Urrutia R. DNA microarrays: revolutionary insight into the living genome. Surgery 2001;130:403-7.
90. Zhou W, Sokoll LJ, Bruzek DJ, Zhang L, Velculescu V, Goldin SB et al. Identifying markers for pancreatic cancer by gene expression analysis. Cancer Epidemiol Biomarkers Prev 1998;7:109-12.
91. Iacobuzio-Donahue CA, Brown PO, Olsen M, Maitra A, Walter K, Jaffee E et al. Exploration of global gene expression of pancreatic adenocarcinoma by cDNA microarray analysis. Manuscript in preparation 2002.
92. Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, Meyer R et al. Discovery if novel tumor markers of pancreatic cancer using global gene expression technology. Am J Pathol. In press 2002.
93. Rosty C, Christa L, Kuzdzal S, Baldwin WM, Zahurak ML, Carnot F et al. Identification of Hepatocarcinoma-Intestine-Pancreas/Pancreatitis-Associated Protein-1 (HIP/PAP-1) as a biomarker for pancreatic adenocarcinoma by protein biochip technology. Cancer Res. In press 2002.