Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development

Jian Wu, Hanno Matthaei, Anirban Maitra, Marco Dal Molin, Laura D. Wood, James R. Eshleman, Michael Goggins, Marcia I. Canto, Richard D. Schulick, Barish H. Edil, Christopher L. Wolfgang, Alison P. Klein, Luis A. Diaz, Peter J. Allen, C. Schmidt, Kenneth W. Kinzler, Nickolas Papadopoulos, Ralph H. Hruban, Bert Vogelstein

Research output: Contribution to journalArticle

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Abstract

More than 2% of the adult U.S. population harbors a pancreatic cyst. These often pose a difficult management problem because conventional criteria cannot always distinguish cysts with malignant potential from those that are innocuous. One of the most common cystic neoplasms of the pancreas, and a bona fide precursor to invasive adenocarcinoma, is called intraductal papillary mucinous neoplasm (IPMN). To help reveal the pathogenesis of these lesions, we purified the DNA from IPMN cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. In addition to the expected KRAS mutations, we identified recurrent mutations at codon 201 of GNAS. A larger number (113) of additional IPMNs were then analyzed to determine the prevalence of KRAS and GNAS mutations. In total, we found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. In addition to defining a new pathway for pancreatic neoplasia, these data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.

Original languageEnglish
Article number92ra66
JournalScience Translational Medicine
Volume3
Issue number92
DOIs
StatePublished - Jul 20 2011

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Pancreatic Cyst
Mutation
Adenocarcinoma
Pancreatic Neoplasms
Neoplasms
Cyst Fluid
Codon
Cysts

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wu, J., Matthaei, H., Maitra, A., Dal Molin, M., Wood, L. D., Eshleman, J. R., ... Vogelstein, B. (2011). Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Science Translational Medicine, 3(92), [92ra66]. https://doi.org/10.1126/scitranslmed.3002543

Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. / Wu, Jian; Matthaei, Hanno; Maitra, Anirban; Dal Molin, Marco; Wood, Laura D.; Eshleman, James R.; Goggins, Michael; Canto, Marcia I.; Schulick, Richard D.; Edil, Barish H.; Wolfgang, Christopher L.; Klein, Alison P.; Diaz, Luis A.; Allen, Peter J.; Schmidt, C.; Kinzler, Kenneth W.; Papadopoulos, Nickolas; Hruban, Ralph H.; Vogelstein, Bert.

In: Science Translational Medicine, Vol. 3, No. 92, 92ra66, 20.07.2011.

Research output: Contribution to journalArticle

Wu, J, Matthaei, H, Maitra, A, Dal Molin, M, Wood, LD, Eshleman, JR, Goggins, M, Canto, MI, Schulick, RD, Edil, BH, Wolfgang, CL, Klein, AP, Diaz, LA, Allen, PJ, Schmidt, C, Kinzler, KW, Papadopoulos, N, Hruban, RH & Vogelstein, B 2011, 'Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development', Science Translational Medicine, vol. 3, no. 92, 92ra66. https://doi.org/10.1126/scitranslmed.3002543
Wu, Jian ; Matthaei, Hanno ; Maitra, Anirban ; Dal Molin, Marco ; Wood, Laura D. ; Eshleman, James R. ; Goggins, Michael ; Canto, Marcia I. ; Schulick, Richard D. ; Edil, Barish H. ; Wolfgang, Christopher L. ; Klein, Alison P. ; Diaz, Luis A. ; Allen, Peter J. ; Schmidt, C. ; Kinzler, Kenneth W. ; Papadopoulos, Nickolas ; Hruban, Ralph H. ; Vogelstein, Bert. / Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. In: Science Translational Medicine. 2011 ; Vol. 3, No. 92.
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