Skip to main content
SpringerLink
Log in

PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Background and aims

Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-α (PIK3CA) gene in various human tumors. Three hot-spot mutations in the exons 9 and 20 have been proven to activate the Akt signalling pathway. The Raf/MEK/ERK (mitogen-activated protein kinase) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Here we evaluate the mutational status of PIK3CA, KRAS, and BRAF in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMNC) of the pancreas.

Materials and methods

Exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 of PIK3CA, exons 1 of KRAS, and exons 5, 11, and 15 of BRAF were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing.

Results

We identified four somatic missense mutations of PIK3CA within the 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported to be a hot-spot mutation. Furthermore, we found 17 (47%) KRAS mutations in exon 1 and one missense mutation (2.7%) in exon 15 of BRAF.

Conclusion

This data is the first report of PIK3CA mutation in pancreatic cancer and it appears to be the first oncogene to be mutated in IPMN/IPMC but not in conventional ductal adenocarcinoma of the pancreas. Our data provide evidence that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, Biankin SA, Compton C, Fukushima N, Furukawa T (2004) An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol 28(8):977–987

    Article  PubMed  Google Scholar 

  2. Kloppel GSE, Longnecker DS (1996) Histological typing of tumours of the exocrine pancreas. New York

  3. D’Angelica M, Brennan MF, Suriawinata AA, Klimstra D, Conlon KC (2004) Intraductal papillary mucinous neoplasms of the pancreas: an analysis of clinicopathologic features and outcome. Ann Surg 239(3):400–408

    Article  PubMed  Google Scholar 

  4. Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD (2004) Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg 239(6):788–797 discussion 797–789

    Article  PubMed  Google Scholar 

  5. Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS (2002) Intraductal papillary-mucinous neoplasms of the pancreas: an analysis of in situ and invasive carcinomas in 28 patients. Cancer 94(1):62–77

    Article  PubMed  Google Scholar 

  6. Salvia R, Fernandez-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P, Warshaw AL (2004) Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg 239(5):678–685 discussion 685–677

    Article  PubMed  Google Scholar 

  7. Adsay NV, Merati K, Andea A, Sarkar F, Hruban RH, Wilentz RE, Goggins M, Iocobuzio-Donahue C, Longnecker DS, Klimstra DS (2002) The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis. Mod Path 15(10):1087–1095

    Article  Google Scholar 

  8. Raimondo M, Tachibana I, Urrutia R, Burgart LJ, DiMagno EP (2002) Invasive cancer and survival of intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol 97(10):2553–2558

    Article  PubMed  Google Scholar 

  9. Maire F, Hammel P, Terris B, Paye F, Scoazec JY, Cellier C, Barthet M, O’Toole D, Rufat P, Partensky C (2002) Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma. Gut 51(5):717–722

    Article  PubMed  CAS  Google Scholar 

  10. Hermanova M, Lukas Z, Nenutil R, Brazdil J, Kroupova I, Kren L, Pazourkova M, Ruzicka M, Dite P (2004) Amplification and overexpression of HER-2/neu in invasive ductal carcinomas of the pancreas and pancreatic intraepithelial neoplasms and the relationship to the expression of p21(WAF1/CIP1). Neoplasma 51(2):77–83

    PubMed  CAS  Google Scholar 

  11. Yamao K, Ohashi K, Nakamura T, Suzuki T, Shimizu Y, Nakamura Y, Horibe Y, Yanagisawa A, Nakao A, Nimuara Y (2000) The prognosis of intraductal papillary mucinous tumors of the pancreas. Hepatogastroenterology 47(34):1129–1134

    PubMed  CAS  Google Scholar 

  12. Chari ST, Yadav D, Smyrk TC, DiMagno EP, Miller LJ, Raimondo M, Clain JE, Norton IA, Pearson RK, Petersen BT (2002) Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology 123(5):1500–1507

    Article  PubMed  Google Scholar 

  13. Nakagohri T, Konishi M, Inoue K, Tanizawa Y, Kinoshita T (2004) Invasive carcinoma derived from intraductal papillary mucinous carcinoma of the pancreas. Hepatogastroenterology 51(59):1480–1483

    PubMed  Google Scholar 

  14. Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD (2001) Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 17:615–675

    Article  PubMed  CAS  Google Scholar 

  15. Domin J, Waterfield MD (1997) Using structure to define the function of phosphoinositide 3-kinase family members. FEBS Lett 410(1):91–95

    Article  PubMed  CAS  Google Scholar 

  16. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501

    Article  PubMed  CAS  Google Scholar 

  17. Carpenter CL, Duckworth BC, Auger KR, Cohen B, Schaffhausen BS, Cantley LC (1990) Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem 265(32):19704–19711

    PubMed  CAS  Google Scholar 

  18. Wymann MP, Pirola L (1998) Structure and function of phosphoinositide 3-kinases. Biochim Biophys Acta 1436(1–2):127–150

    PubMed  CAS  Google Scholar 

  19. Vanhaesebroeck B, Waterfield MD (1999) Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 253(1):239–254

    Article  PubMed  CAS  Google Scholar 

  20. Kodaki T, Woscholski R, Hallberg B, Rodriguez-Viciana P, Downward J, Parker PJ (1994) The activation of phosphatidylinositol 3-kinase by Ras. Curr Biol 4(9):798–806

    Article  PubMed  CAS  Google Scholar 

  21. Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J (1996) Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J 15(10):2442–2451

    PubMed  CAS  Google Scholar 

  22. Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF (1992) Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. Cell 70(3):419–429

    Article  PubMed  CAS  Google Scholar 

  23. Whitman M, Downes CP, Keeler M, Keller T, Cantley L (1988) Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332(6165):644–646

    Article  PubMed  CAS  Google Scholar 

  24. Vanhaesebroeck B, Alessi DR (2000) The PI3K-PDK1 connection: more than just a road to PKB. Biochem J 346(Pt 3):561–576

    Article  PubMed  CAS  Google Scholar 

  25. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304(5670):554

    Article  PubMed  CAS  Google Scholar 

  26. Campbell IG, Russell SE, Choong DY, Montgomery KG, Ciavarella ML, Hooi CS, Cristiano BE, Pearson RB, Phillips WA (2004) Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64(21):7678–7681

    Article  PubMed  CAS  Google Scholar 

  27. Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH (2005) PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 24(8):1477–1480

    Article  PubMed  CAS  Google Scholar 

  28. Broderick DK, Di C, Parrett TJ, Samuels YR, Cummins JM, McLendon RE, Fults DW, Velculescu VE, Bigner DD, Yan H (2004) Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res 64(15):5048–5050

    Article  PubMed  CAS  Google Scholar 

  29. Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair BG, Lin C (2004) The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther 3(8):772–775

    Article  PubMed  CAS  Google Scholar 

  30. Qiu W, Schonleben F, Li X, Ho DJ, Close LG, Manolidis S, Bennett BP, Su GH (2006) PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 12(5):1441–1446

    Article  PubMed  CAS  Google Scholar 

  31. Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, So S, Chen X, Yuen ST, Leung SY (2005) Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer 5(1):29

    Article  PubMed  CAS  Google Scholar 

  32. Laud K, Kannengiesser C, Avril MF, Chompret A, Stoppa-Lyonnet D, Desjardins L, Eychene A, Demenais F, Lenoir GM, Bressac-de Paillerets B (2003) BRAF as a melanoma susceptibility candidate gene? Cancer Res 63(12):3061–3065

    PubMed  CAS  Google Scholar 

  33. Peyssonnaux C, Eychene A (2001) The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell 93(1–2):53–62

    Article  PubMed  CAS  Google Scholar 

  34. Dhillon AS, Meikle S, Peyssonnaux C, Grindlay J, Kaiser C, Steen H, Shaw PE, Mischak H, Eychene A, Kolch W (2003) A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation. Mol Cell Biol 23(6):1983–1993

    Article  PubMed  CAS  Google Scholar 

  35. Aguirre-Ghiso JA, Estrada Y, Liu D, Ossowski L (2003) ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res 63(7):1684–1695

    PubMed  CAS  Google Scholar 

  36. Rul W, Zugasti O, Roux P, Peyssonnaux C, Eychene A, Franke TF, Lenormand P, Fort P, Hibner U (2002) Activation of ERK, controlled by Rac1 and Cdc42 via Akt, is required for anoikis. Ann N Y Acad Sci 973:145–148

    Article  PubMed  CAS  Google Scholar 

  37. Smalley KS (2003) A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int J Cancer 104(5):527–532

    Article  PubMed  CAS  Google Scholar 

  38. Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62(23):6997–7000

    PubMed  CAS  Google Scholar 

  39. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954

    Article  PubMed  CAS  Google Scholar 

  40. Naoki K, Chen TH, Richards WG, Sugarbaker DJ, Meyerson M (2002) Missense mutations of the BRAF gene in human lung adenocarcinoma. Cancer Res 62(23):7001–7003

    PubMed  CAS  Google Scholar 

  41. Dong J, Phelps RG, Qiao R, Yao S, Benard O, Ronai Z, Aaronson SA (2003) BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res 63(14):3883–3885

    PubMed  CAS  Google Scholar 

  42. Singer G, Oldt R 3rd, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih Ie M (2003) Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 95(6):484–486

    Article  PubMed  CAS  Google Scholar 

  43. Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C (2003) Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab 88(6):2745–2752

    Article  PubMed  CAS  Google Scholar 

  44. Z’Graggen K, Rivera JA, Compton CC, Pins M, Werner J, Fernandez-del Castillo C, Rattner DW, Lewandrowski KB, Rustgi AK, Warshaw AL (1997) Prevalence of activating K-ras mutations in the evolutionary stages of neoplasia in intraductal papillary mucinous tumors of the pancreas. Ann Surg 226(4):491–498 discussion 498–500

    Article  PubMed  CAS  Google Scholar 

  45. Satoh K, Shimosegawa T, Moriizumi S, Koizumi M, Toyota T (1996) K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas. Pancreas 12(4):362–368

    Article  PubMed  CAS  Google Scholar 

  46. Satoh K, Sawai T, Shimosegawa T, Koizumi M, Yamazaki T, Mochizuki F, Toyota T (1993) The point mutation of c-Ki-ras at codon 12 in carcinoma of the pancreatic head region and in intraductal mucin-hypersecreting neoplasm of the pancreas. Int J Pancreatol 14(2):135–143

    PubMed  CAS  Google Scholar 

  47. Sessa F, Solcia E, Capella C, Bonato M, Scarpa A, Zamboni G, Pellegata NS, Ranzani GN, Rickaert F, Kloppel G (1994) Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch 425(4):357–367

    Article  PubMed  CAS  Google Scholar 

  48. Tada M, Omata M, Ohto M (1991) Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases. Cancer 67(3):634–637

    Article  PubMed  CAS  Google Scholar 

  49. Yanagisawa A, Kato Y, Ohtake K, Kitagawa T, Ohashi K, Hori M, Takagi K, Sugano H (1991) c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas. Jpn J Cancer Res 82(10):1057–1060

    PubMed  CAS  Google Scholar 

  50. Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Goggins M (2001) STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 159(6):2017–2022

    PubMed  CAS  Google Scholar 

  51. Sahin F, Maitra A, Argani P, Sato N, Maehara N, Montgomery E, Goggins M, Hruban RH, Su GH (2003) Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms. Mod Path 16(7):686–691

    Article  Google Scholar 

  52. Fujii H, Inagaki M, Kasai S, Miyokawa N, Tokusashi Y, Gabrielson E, Hruban RH (1997) Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 151(5):1447–1454

    PubMed  CAS  Google Scholar 

  53. Sato N, Ueki T, Fukushima N, Iacobuzio-Donahue CA, Yeo CJ, Cameron JL, Hruban RH, Goggins M (2002) Aberrant methylation of CpG islands in intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology 123(1):365–372

    Article  PubMed  CAS  Google Scholar 

  54. House MG, Guo M, Iacobuzio-Donahue C, Herman JG (2003) Molecular progression of promoter methylation in intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Carcinogenesis 24(2):193–198

    Article  PubMed  CAS  Google Scholar 

  55. Yuen ST, Davies H, Chan TL, Ho JW, Bignell GR, Cox C, Stephens P, Edkins S, Tsui WW, Chan AS (2002) Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 62(22):6451–6455

    PubMed  CAS  Google Scholar 

  56. Kang S, Bader AG, Vogt PK (2005) Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA 102(3):802–807

    Article  PubMed  CAS  Google Scholar 

  57. Benes CH, Wu N, Elia AE, Dharia T, Cantley LC, Soltoff SP (2005) The C2 domain of PKCdelta is a phosphotyrosine binding domain. Cell 121(2):271–280

    Article  PubMed  CAS  Google Scholar 

  58. Wang Y, Helland A, Holm R, Kristensen GB, Borresen-Dale AL (2005) PIK3CA mutations in advanced ovarian carcinomas. Hum Mutat 25(3):322

    Article  PubMed  CAS  Google Scholar 

  59. Gallmeier E, Calhoun ES, Kern SE (2004) No mutations in PIK3CA identified in pancreatic carcinoma. NOGO 8:2

    Google Scholar 

  60. Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N (2001) Kirsten ras mutations in patients with colorectal cancer: the ‘‘RASCAL II’’ study. Br J Cancer 85(5):692–696

    Article  PubMed  CAS  Google Scholar 

  61. Motojima K, Urano T, Nagata Y, Shiku H, Tsurifune T, Kanematsu T (1993) Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma. Ann Surg 217(2):138–143

    Article  PubMed  CAS  Google Scholar 

  62. Moskaluk CA, Hruban RH, Kern SE (1997) p16 and K-ras mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res 57:2140–2143

    PubMed  CAS  Google Scholar 

  63. Rozenblum E, Schutte M, Goggins M, Hahn SA, Lu J, Panzer S, Zahurak M, Goodman SN, Hruban RH, Yeo CJ (1997) Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res 57:1731–1734

    PubMed  CAS  Google Scholar 

  64. Longnecker DS, Adsay NV, Fernandez-del Castillo C, Hruban RH, Kasugai T, Klimstra DS, Kloppel G, Luttges J, Memoli VA, Tosteson TD (2005) Histopathological diagnosis of pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms: interobserver agreement. Pancreas 31(4):344–349

    Article  PubMed  Google Scholar 

  65. Furukawa T, Kloppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, Hruban RH, Kato Y, Klimstra DS, Longnecker DS (2005) Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study. Virchows Arch 447(5):794–799

    Article  PubMed  Google Scholar 

  66. Sommerer F, Hengge UR, Markwarth A, Vomschloss S, Stolzenburg JU, Wittekind C, Tannapfel A (2005) Mutations of BRAF and RAS are rare events in germ cell tumours. Int J Cancer 113(2):329–335

    Article  PubMed  CAS  Google Scholar 

  67. Weber A, Langhanki L, Sommerer F, Markwarth A, Wittekind C, Tannapfel A (2003) Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 22(30):4757–4759

    Article  PubMed  CAS  Google Scholar 

  68. Calhoun ES, Jones JB, Ashfaq R, Adsay V, Baker SJ, Valentine V, Hempen PM, Hilgers W, Yeo CJ, Hruban RH (2003) BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am J Pathol 163(4):1255–1260

    PubMed  CAS  Google Scholar 

  69. Ishimura N, Yamasawa K, Karim Rumi MA, Kadowaki Y, Ishihara S, Amano Y, Nio Y, Higami T, Kinoshita Y (2003) BRAF and K-ras gene mutations in human pancreatic cancers. Cancer Lett 199(2):169–173

    Article  PubMed  CAS  Google Scholar 

  70. Zhang BH, Guan KL (2000) Activation of B-Raf kinase requires phosphorylation of the conserved residues Thr598 and Ser601. EMBO J 19(20):5429–5439

    Article  PubMed  CAS  Google Scholar 

  71. Sasaki S, Yamamoto H, Kaneto H, Ozeki I, Adachi Y, Takagi H, Matsumoto T, Itoh H, Nagakawa T, Miyakawa H (2003) Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. Oncol Rep 10(1):21–25

    PubMed  CAS  Google Scholar 

  72. Biankin AV, Biankin SA, Kench JG, Morey AL, Lee CS, Head DR, Eckstein RP, Hugh TB, Henshall SM, Sutherland RL (2002) Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma. Gut 50(6):861–868

    Article  PubMed  CAS  Google Scholar 

  73. Fukushima N, Sato N, Sahin F, Su GH, Hruban RH, Goggins M (2003) Aberrant methylation of suppressor of cytokine signalling-1 (SOCS-1) gene in pancreatic ductal neoplasms. Br J Cancer 89(2):338–343

    Article  PubMed  CAS  Google Scholar 

  74. Matsubayashi H, Sato N, Fukushima N, Yeo CJ, Walter KM, Brune K, Sahin F, Hruban RH, Goggins M (2003) Methylation of cyclin D2 is observed frequently in pancreatic cancer but is also an age-related phenomenon in gastrointestinal tissues. Clin Cancer Res 9(4):1446–1452

    PubMed  CAS  Google Scholar 

  75. Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ (1999) Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 154(6):1835–1840

    PubMed  CAS  Google Scholar 

  76. Iacobuzio-Donahue CA, Klimstra DS, Adsay NV, Wilentz RE, Argani P, Sohn TA, Yeo CJ, Cameron JL, Kern SE, Hruban RH (2000) Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: comparison with conventional ductal adenocarcinomas. Am J Pathol 157(3):755–761

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, Friedrich-Alexander-University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Frank Schönleben & Werner Hohenberger

  2. Department of Otolaryngology/Head and Neck Surgery, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Frank Schönleben, Wanglong Qiu & Gloria H. Su

  3. Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Helen E. Remotti & Gloria H. Su

Authors
  1. Frank Schönleben
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanglong Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helen E. Remotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Werner Hohenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gloria H. Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank Schönleben.

Additional information

German Society of Surgery, Surgical Forum 2008, Best Abstracts

This work was supported by the National Cancer Institute (NCI) Temin Award CA95434 and the NCI R01 CA109525 (GHS).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schönleben, F., Qiu, W., Remotti, H.E. et al. PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas. Langenbecks Arch Surg 393, 289–296 (2008). https://doi.org/10.1007/s00423-008-0285-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-008-0285-7

Keywords

Search

Navigation