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Molecular Genetics of Pancreatic Carcinoma

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Pancreatic Cancer

Abstract

The application of modern molecular biological techniques to the study of human tumors in the past two decades has demonstrated that cancer is a genetic disease. Strucalterations in genomic DNA (point mutation, gene rearrangement, and gene deletion), which result in alterations in protein coding sequences or their expression, have been found in every human neoplasm studied. The finding of these genetic alterations in invasive cancers and in their histologically identifiable neoplastic precursor lesions, but not in the nonneoplastic tissues from which they arose, is consistent with the theory that neoplastic progression is the result of the clonal evolution of cellular populations accompanying a selection for mutations (1,2). Germ-line mutations in specific genes are also responsible for many cases in which there is a familial predisposition to cancer (3), further underscoring the genetic basis of cancer.

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References

  1. Nowell P. Molecular events in tumor development, N Engl J Med 1988; 319:575–577.

    Article  PubMed  CAS  Google Scholar 

  2. Kern SE. Clonality: more than just a tumor-progression model. J Natl Cancer Inst 1993; 85:1020–1021.

    Article  PubMed  CAS  Google Scholar 

  3. Knudson AG. Antioncogenes and human cancer. Proc Natl Acad Sci USA 1993; 90: 10,914–10,921.

    Article  PubMed  CAS  Google Scholar 

  4. Knudson AG. Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol 1996; 122:135–140.

    Article  PubMed  CAS  Google Scholar 

  5. Almoguerra C, Shibata D, Forrester K, Martin J, Arnheim N, and Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988; 53:549–554.

    Article  Google Scholar 

  6. Hruban RH, van Mansfeld ADM, Offerhaus GJA, van Weering DHJ, Allison DC, Goodman SN, et al. K-ras oncogene activation in adenocarcinomas 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; 143:545–554.

    PubMed  CAS  Google Scholar 

  7. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 1989; 49:4682–4689.

    PubMed  CAS  Google Scholar 

  8. Maruta H and Burgess AW. Regulation of the Ras signalling network: bioessays. 1994; 16:489–496.

    PubMed  CAS  Google Scholar 

  9. Yamada H, Sakamoto H, Taira M, Nishimura S, Shimosato Y, Terada M, and Sugimura T. Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes. Jpn J Cancer Res 1986; 77:370–375.

    PubMed  CAS  Google Scholar 

  10. Johansson B, Bardi G, Heim S, Mandahl N, Mertens F, Bak-Jensen E, Andren-Sandberg A, and Mitelman F. Nonrandom chromosomal rearrangements in pancreatic carcinomas. Cancer 1992; 69:1–8.

    Article  Google Scholar 

  11. Griffin CA, Hruban RH, Morsberger LA, Ellingham T, Long PP, Jaffee EM, et al. Consistent chromosome abnormalities in adenocarcinoma of the pancreas. Cancer Res 1995; 55:2394–2399.

    PubMed  CAS  Google Scholar 

  12. Griffin CA, Hruban RH, Long PP, Morsberger LA, Douna-Issa F, and Yeo CJ. Chromosome abnormalities in pancreatic adenocarcinoma. Genes, Chrom, Cancer 1994; 9:93–100.

    Article  CAS  Google Scholar 

  13. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, and Testa JR. Amplification of AKT2 in human pancreatic cancer cells and inhibition of AKT2 expression and tumorigenecity by antisense RNA. Proc Natl Acad Sci USA 1996; 93:3636–3641.

    Article  PubMed  CAS  Google Scholar 

  14. Berrozpe G, Schaeffer J, Peinado MA, Reak FS, and Perucho M. Comparative analysis of mutations in the p53 and K-ras genes in pancreatic cancer. Int J Cancer 1994; 58:185–191.

    Article  PubMed  CAS  Google Scholar 

  15. Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, and Kern SE. p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopoly-mer tracts in DNA microdeletions. Cancer Res 1994; 54:3025–3033.

    PubMed  CAS  Google Scholar 

  16. Suwa H, Yoshimura T, Yamaguchi N, Kanehira K, Manabe T, Imamura M, Hiai H, and Fukumoto M. K-ras and p53 alterations in genomic DNA and transcripts of human pancreatic adenocarcinoma cell lines. Jpn J Cancer Res 1994; 85:1005–1014.

    Article  PubMed  CAS  Google Scholar 

  17. Ruggeri B, Zhang SY, Caamano J, DiRado M, Flynn SD, and Klein-Szanto AJP. Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes. Oncogene 1992; 7:1503–1511.

    PubMed  CAS  Google Scholar 

  18. Simon B, Weinel R, Höhne M, Watz J, Schmidt J, Körtner G, and Arnold R. Frequent alterations of the tumor suppressor genes p53 and DCC in human pancreatic carcinoma. Gastroenterology 1994; 106:1645–1651.

    PubMed  CAS  Google Scholar 

  19. Rozenblum E, Schutte M, Goggins M, Hahn SA, Lu J, Panzer S, et al. Natural relationships among tumor-suppressive pathways: application of pancreatic cancer model. Cancer Res 1997; 57:1731–1734.

    PubMed  CAS  Google Scholar 

  20. Pellegata S, Sessa F, Renault B, Bonato M, Leone BE, Solcia E, and Ranzani GN. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res 1994; 54:1556–1560.

    PubMed  CAS  Google Scholar 

  21. Weyrer K, Feichtinger H, Haun M, Weiss G, Ofner D, Weger AR, Umlauft F, and Grunewald K. p53, Ki-ras, and DNA ploidy in human pancreatic ductal adenocarcinomas. Lab Invest 1996; 74:279–289.

    PubMed  CAS  Google Scholar 

  22. Scarpa A, Capelli P, Mukai K, Zamboni G, Oda T, Iacono C, and Hirohashi S. Pancreatic adenocarcinomas frequently show p53 gene mutations. Am J Pathol 1993; 142:1534–1543.

    PubMed  CAS  Google Scholar 

  23. Nakamori S, Yashima K, Murakami Y, Ishikawa O, Ohigashi H, Imaoka S, et al. Association of p53 gene mutations with short survival in pancreatic adenocarcinoma. Jpn J Cancer Res 1995; 86:174–181.

    Article  PubMed  CAS  Google Scholar 

  24. Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Buchler M, Beger HG, and Korc M. p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Lett 1993; 69:151–160.

    Article  PubMed  CAS  Google Scholar 

  25. Seymour AB, Hruban RH, Redston M, Caldas C, Powell SM, Kinzler KW, Yee CJ, and Kern SE. Allelotype of pancreatic adenocarcinoma. Cancer Res 1994; 54:2761–2764.

    PubMed  CAS  Google Scholar 

  26. Kern SE, Pietenpol JA, Thiagalingam S, Seymour A, Kinzler KW, and Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science 1992; 256:827–830.

    Article  PubMed  CAS  Google Scholar 

  27. Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, and Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science 1991; 252:1708–1711.

    Article  PubMed  CAS  Google Scholar 

  28. Kern SE, Kinzler KW, Baker SJ, Nigro JM, Rotter V, Levine AJ, et al. Mutant p53 proteins bind DNA abnormally in vitro. Oncogene 1991; 6:131–136.

    PubMed  CAS  Google Scholar 

  29. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, and Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51:6304–6311.

    PubMed  CAS  Google Scholar 

  30. Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, and Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 1991; 352:345–347.

    Article  PubMed  CAS  Google Scholar 

  31. 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. Nature Genetics 1994; 8:27–31.

    Article  PubMed  CAS  Google Scholar 

  32. Naumann M, Savitskaia N, Eilert C, Schramm A, Kalthoff H, and Schmiegel W. Frequent codeletion of pl6/MTS1 and p15/MTS2 and genetic alterations in pl6/MTSl in pancreatic tumors. Gastroenterology 1996; 110:1215–1224.

    Article  PubMed  CAS  Google Scholar 

  33. Liu Q, Yan YX, McClure M, Nakagawa H, Fujimura F, and Rustgi AK. MTS-1 (CDKN2) tumor suppressor gene deletions are a frequent event in esophagus squamous cancer and pancreatic adenocarcinoma cell lines. Oncogene 1995; 10:619–622.

    PubMed  CAS  Google Scholar 

  34. Bartsch D, Shevlin DW, Tung WS, Kisker O, Wells SAJ, and Goodfellow PJ. Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas. Genes Chromosom Cancer 1995; 14:189–195.

    Article  PubMed  CAS  Google Scholar 

  35. Yang R, Gombart AF, Serrano M, and Koeffler HP. Mutational effects on the pl6INK4a tumor suppressor protein. Cancer Res 1995; 55:2503–2506.

    PubMed  CAS  Google Scholar 

  36. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994; 264:436–440.

    Article  PubMed  CAS  Google Scholar 

  37. Jen J, Harper JW, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S, et al. Deletion of p16 and p15 genes in brain tumors. Cancer Res 1994; 54:6353–6358.

    PubMed  CAS  Google Scholar 

  38. Rozenblum E, Schutte M, and Kern SE. INK4 genes in pancreatic carcinoma. Oncol Rep 1996; 3:743–745.

    PubMed  CAS  Google Scholar 

  39. Wölfel T, Hauer M, Schneider J, Serrano M, Wölfel C, Klehmann-Hieb E, et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 1995; 269:1281–1284.

    Article  PubMed  Google Scholar 

  40. Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, Walker GJ, et al. Germline mutations in the pl6INK4a binding domain of CDK4 in familial melanoma. Nature Genet 1996; 12:97–99.

    Article  PubMed  CAS  Google Scholar 

  41. Moskaluk CA, Hruban RH, Lietman AS, Smyrk T, Fusaro L, Fusaro R, et al. Novel germline pl6INK4a mutation in familial pancreatic carcinoma. Hum Mutat (in press), 1998.

    Google Scholar 

  42. Hahn SA, Seymour AB, Hoque ATMS, Schutte M, da Costa LT, Redston MS, et al. Allelotype of pancreatic adenocarcinoma using a xenograft model. Cancer Res 1995; 55:4670–4675.

    PubMed  CAS  Google Scholar 

  43. Hahn SA, Hoque ATMS, Moskaluk CA, daCosta LT, Schutte M, Rozenblum E, et al. Homozygous deletion map at 18q21.1 in pancreatic cancer. Cancer Res 1996; 56:490–494.

    PubMed  CAS  Google Scholar 

  44. Sekelsky JJ, Newfeld SJ, Raftery LA, Chartoff EH, and Gelbart WM. Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 1995; 139:1347–1358.

    PubMed  CAS  Google Scholar 

  45. Liu F, Hata A, Baker JC, Doody J, Carcamo J, Harland RM, and Massague J. A human Mad protein acting as a BMP-regulated transcriptional activator. Nature 1996; 381:620–623.

    Article  PubMed  CAS  Google Scholar 

  46. Alexandrow MG and Moses HL. Transforming growth factor beta and cell cycle regulation. Cancer Res 1995; 55:1452–1457.

    PubMed  CAS  Google Scholar 

  47. Hoque ATMS, Hahn SA, Schutte M, and Kern SE. DPC4 gene mutation in colitis-associated neoplasia. Gut (in press), 1996.

    Google Scholar 

  48. Thiagalingam S, Lengauer C, Leach FS, Schutte M, Hahn SA, Overhauser J, et al. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet 1996; 13:343–346.

    Article  PubMed  CAS  Google Scholar 

  49. Schutte M, Hruban RH, Hedrick L, Molnar’Nadasdy G, Weinstein CL, Bova GS, et al. DPC4 in various tumor types. Cancer Res 1996; 56:2527–2530.

    PubMed  CAS  Google Scholar 

  50. Nagatake M, Takagi Y, Osada N, Uchida K, Mitsudomi T, Saji S, et al. Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers. Cancer Res 1996; 56:2718–2720.

    PubMed  CAS  Google Scholar 

  51. Kim SK, Fan Y, Papadimitrakopoulou V, Clayman G, Hittleman WN, Hong WK, Lotan R, and Mao L. DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma. Cancer Res 1996; 56:2519–2521.

    PubMed  CAS  Google Scholar 

  52. Barrett MT, Schutte M, Kern SE, and Reid BJ. Allelic loss and mutational analysis of the DPC4 gene in esophageal adenocarcinoma. Cancer Res (in press), 1996.

    Google Scholar 

  53. 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; 52:6696–6698.

    PubMed  CAS  Google Scholar 

  54. McKie AB, Filipe ML, and Lemoine NR. Abnormalities affecting the APC and MCC tumour suppressor gene loci on chromosome 5q occur frequently in gastric cancer but not in pancreatic cancer. Int J Cancer 1993; 55:598–603.

    Article  PubMed  CAS  Google Scholar 

  55. Yashima K, Nakamori S, Murakami Y, Yamaguchi A, Hayashi K, Ishikawa O, Konishi Y, and Sekiya T. Mutations of the adenomatous polyposis coli gene in the mutation cluster region: comparison of human pancreatic and colorectal cancers. Int J Cancer 1994; 59:43–47.

    Article  PubMed  CAS  Google Scholar 

  56. Barton CM, McKie AB, Hogg A, Bia B, Elia G, Phillips SM, Ding SF, and Lemoine NR. Abnormalities of the RBI and DCC tumor suppressor genes: uncommon in human pancreatic adenocarcinoma. Mol Carcinog 1995; 13:61–69.

    Article  PubMed  CAS  Google Scholar 

  57. Huang L, Lang D, Geradts J, Obara T, Klein-Szanto AJ, Lynch HT, and Ruggeri BA. Molecular and immunochemical analyses of RBI and cyclin Dl in human ductal pancreatic carcinomas and cell lines. Mol Carcinog 1996; 15:85–95.

    Article  PubMed  CAS  Google Scholar 

  58. 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; 271:350–353.

    Article  PubMed  CAS  Google Scholar 

  59. Höhne MW, Halatsch M-E, Kahl GE, and Weinel RJ. Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma. Cancer Res 1992;52:2616–2619.

    Google Scholar 

  60. Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, et al. Mad-related genes in the human. Nat Genet 1996; 13:347–349.

    Article  PubMed  CAS  Google Scholar 

  61. Schutte M, da Costa LT, Hahn SA, Moskaluk C, Hoque ATMS, Rozenblum E, et al. A ho-mozygous deletion identified by representational difference analysis in pancreatic carcinoma overlaps the BRCA2 region. Proc Natl Acad Sci USA 1995; 92:5950–5954.

    Article  PubMed  CAS  Google Scholar 

  62. Schutte M, Rozenblum E, Moskaluk CA, Guan X, Hoque ATMS, Hahn SA, et al. An integrated high-resolution physical map of the DPC/BRCA2 region at chromosome 13ql2-13. Cancer Res 1995; 55:4570–4574.

    PubMed  CAS  Google Scholar 

  63. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378:789–792.

    Article  PubMed  CAS  Google Scholar 

  64. Chen Z-H, Zhang H, and Savarese TM. Gene deletion chemoselectivity: codeletion of the genes for pl61NK4, methylthioadenosine phosphorylase, and the α-and β-interferons in human pancreatic cell carcinoma lines and its implications for chemotherapy. Cancer Res 1996; 56:1083–1090.

    PubMed  CAS  Google Scholar 

  65. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75:817–825.

    Article  PubMed  CAS  Google Scholar 

  66. Modrich P. Mismatch repair, genetic stability, and cancer. Science 1994; 266:1959–1960.

    Article  PubMed  CAS  Google Scholar 

  67. Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, et al. Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet 1995; 9:48–55.

    Article  PubMed  CAS  Google Scholar 

  68. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, and Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993; 363:558–561.

    Article  PubMed  CAS  Google Scholar 

  69. Aaltonen LA, Peltomäki P, Leach FS, Sistonen P, Pylkkänen L, Mecklin J-P, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993; 260:812–816.

    Article  PubMed  CAS  Google Scholar 

  70. Thibodeau SN, Bren G, and Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993; 260:816–819.

    Article  PubMed  CAS  Google Scholar 

  71. Han H-J, Yanagisawa A, Kato Y, Park J-G, Kato Y, and Nakamura Y. Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res 1993; 53:5087–5089.

    PubMed  CAS  Google Scholar 

  72. Schutte M and Kern SE. The molecular genetics of pancreatic adenocarcinoma. In: Neop-tolemos J. P. and Lemoine N. R. (eds), Pancreatic cancer: molecular and clinical advan ces, Blackwell, Oxford, 1996; pp. 115–132.

    Google Scholar 

  73. Lynch HT, Fusaro L, Smyrk TC, Watson P, Lanspa S, and Lynch JF. Medical genetic study of eight pancreatic cancer-prone families. Cancer Invest 1995; 13:141–149.

    Article  PubMed  CAS  Google Scholar 

  74. World-Wide Web address http://www.med.jhu.edu/pancreas/registry.htm.

  75. Ghadirian P, Boyle P, Simard A, Baillargeon J, Maisonneuve P, and Perret C. Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol 1991; 10:183–195.

    PubMed  CAS  Google Scholar 

  76. Whelan AJ, Bartsch D, and Goodfellow PJ. Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N Engl J Med 1995; 333:975–977.

    Article  PubMed  CAS  Google Scholar 

  77. Goldstein AM, Fraser MC, Struewing JP, Hussussian CJ, Ranade K, Zametkin DP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with pl6INK4 mutations. N Engl J Med 1995; 333:970–974.

    Article  PubMed  CAS  Google Scholar 

  78. Gruis NA, Sandkuiji LA, van der Velden PA, Bergman W, and Frants RR. CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple-mole melanoma (FAMMM) syndrome families. Melanoma Res 1995; 9:169–177.

    Article  Google Scholar 

  79. Ciotti P, Strigini P, and Bianchi-Scarra G. Familial melanoma and pancreatic cancer. N Engl J Med 1996; 334:469–470.

    Article  PubMed  CAS  Google Scholar 

  80. 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; 56:5360–5364.

    PubMed  CAS  Google Scholar 

  81. Berman DB, Costalas J, Schultz DC, Grana G, Daly M, and Godwin AK. A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Askenazi and non-Jewish individuals. Cancer Res 1996; 56:3409–3414.

    PubMed  CAS  Google Scholar 

  82. Phelan CM, Lancaster JM, Tonin P, Gumbs C, Cochran C, Carter R, et al. Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nature Genet 1996; 13:120–122.

    Article  PubMed  CAS  Google Scholar 

  83. Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, et al. A single BRCA2 mutation in male and female breast carcinoma families from Iceland with varied cancer phenotypes. Nature Genet 1996; 13:117–119.

    Article  PubMed  CAS  Google Scholar 

  84. Moskaluk CA, Hruban RH, Schutte M, Lietman AS, Smyrk T, Fusaro L, et al. Genomic sequencing of DPC4 in the analysis of familial pancreatic carcinoma. Diag Mol Pathol 1997; 6:85–90.

    Article  CAS  Google Scholar 

  85. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988; 319:525–532.

    Article  PubMed  CAS  Google Scholar 

  86. Kozuka S, Sassa R, Taki T, Masamoto K, Nagasawa S, Saga S, Hasegawa K, and Takeuchi M. Relation of pancreatic duct hyperplasia to carcinoma. Cancer 1979; 43:1418–1428.

    Article  PubMed  CAS  Google Scholar 

  87. Yanagisawa A, Ohtake K, Ohashi K, Hori M, Kitagawa T, Sugano H, and Kato Y. Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. Cancer Res 1993; 53:953–956.

    PubMed  CAS  Google Scholar 

  88. Caldas C, Hahn SA, Hruban RH, Redston MS, Yeo CJ, and Kern SE. Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res 1994; 54:3568–3573.

    PubMed  CAS  Google Scholar 

  89. DiGiuseppe JA, Hruban RH, Offerhaus GJA, Clement MJ, van den Berg FM, Cameron JL, and van Mansfeld ADM. Detection of K-ras mutations in mucinous pancreatic duct hyperplasia from a patient with a family history of pancreatic carcinoma. Am J Pathol 1994; 144:889–895.

    PubMed  CAS  Google Scholar 

  90. Tabata T, Fujimori T, Maeda S, Yamamoto M, and Saitoh Y. The role of Ras mutation in pancreatic cancer, precancerous lesions, and chronic pancreatitis. Int J Pancreatol 1993; 14:237–244.

    PubMed  CAS  Google Scholar 

  91. Tada M, Ohashi M, Shiratori Y, Okudairi T, Komatsu Y, Kawabe T, et al. Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease. Gas-troenterology 1996; 110:227–231.

    Article  CAS  Google Scholar 

  92. Hoshi T, Imai M, and Ogawa K. Frequent K-ras mutations and absence of p53 mutations in mucin-producing tumors of the pancreas. J Surg Oncol 1994; 55:84–91.

    Article  PubMed  CAS  Google Scholar 

  93. Hoorens A, Lemoine NR, McLellan E, Morohoshi T, Kamisawa T, Heitz PU, et al. Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Kiras mutation. Am J Pathol 1993; 143:685–698.

    CAS  Google Scholar 

  94. Terhune PG, Heffess CS, and Longnecker DS. Only wild-type c-Ki-ras codons 12, 13, and 61 in human pancreatic acinar cell carcinomas. Mol Carcinog 1994; 10:110–114.

    Article  PubMed  CAS  Google Scholar 

  95. Yashiro T, Fulton N, Hara H, Yasuda K, Montag A, Yashiro N, et al. Comparison of mutations of ras oncogene in human pancreatic exocrine and endocrine tumors. Surgery 1993; 114:758–763.

    PubMed  CAS  Google Scholar 

  96. Lynch HT. Genetics and pancreatic cancer. Arch Surg 1994; 129:266–268.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Christopher A. Moskaluk
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  2. Scott E. Kern
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Editors and Affiliations

  1. UCLA School of Medicine, Los Angeles, CA, USA

    Howard A. Reber MD

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Moskaluk, C.A., Kern, S.E. (1998). Molecular Genetics of Pancreatic Carcinoma. In: Reber, H.A. (eds) Pancreatic Cancer. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1810-4_1

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  • DOI: https://doi.org/10.1007/978-1-4612-1810-4_1

  • Publisher Name: Humana Press, Totowa, NJ

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