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Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.
Ann Surg Oncol 2013; 20(12):3802-8AS

Abstract

BACKGROUND

Intraductal papillary mucinous neoplasms (IPMNs) are the most common cystic precursor lesions of invasive pancreatic cancer. The recent identification of activating GNAS mutations at codon 201 in IPMNs is a promising target for early detection and therapy. The purpose of this study was to explore clinicopathological correlates of GNAS mutational status in resected IPMNs.

METHODS

Clinical and pathologic characteristics were retrieved on 54 patients in whom GNAS codon 201 mutational status was previously reported ("historical group", Wu et al. Sci Transl Med 3:92ra66, 2011). In addition, a separate cohort of 32 patients (validation group) was included. After microdissection and DNA extraction, GNAS status was determined in the validation group by pyrosequencing.

RESULTS

GNAS activating mutations were found in 64% of the 32 IPMNs included in the validation group, compared with a previously reported prevalence of 57% in the historical group. Overall, 52 of 86 (61%) of IPMNs demonstrated GNAS mutations in the two studies combined. Analysis of both groups confirmed that demographic characteristics, tumor location, ductal system involvement, focality, size, grade of dysplasia, presence of an associated cancer, and overall survival were not correlated with GNAS mutational status. Stratified by histological subtype, 100% of intestinal type IPMNs demonstrated GNAS mutations compared to 51% of gastric IPMN, 71% of pancreatobiliary IPMNs, and 0% of oncocytic IPMNs.

CONCLUSIONS

GNAS activating mutations can be reliably detected in IPMNs by pyrosequencing. In terms of clinicopathological parameters, only histological subtype was correlated with mutational frequency, with the intestinal phenotype always associated with GNAS mutations.

Authors+Show Affiliations

Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Unit of General Surgery B, Pancreas Institute, Department of Surgery, "G.B. Rossi" Hospital, University of Verona Hospital Trust, Verona, Italy.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany.Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Unit of General Surgery B, Pancreas Institute, Department of Surgery, "G.B. Rossi" Hospital, University of Verona Hospital Trust, Verona, Italy.Unit of General Surgery B, Pancreas Institute, Department of Surgery, "G.B. Rossi" Hospital, University of Verona Hospital Trust, Verona, Italy.Unit of General Surgery B, Pancreas Institute, Department of Surgery, "G.B. Rossi" Hospital, University of Verona Hospital Trust, Verona, Italy.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD.Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23846778

Citation

Molin, Marco Dal, et al. "Clinicopathological Correlates of Activating GNAS Mutations in Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas." Annals of Surgical Oncology, vol. 20, no. 12, 2013, pp. 3802-8.
Molin MD, Matthaei H, Wu J, et al. Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg Oncol. 2013;20(12):3802-8.
Molin, M. D., Matthaei, H., Wu, J., Blackford, A., Debeljak, M., Rezaee, N., ... Maitra, A. (2013). Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Annals of Surgical Oncology, 20(12), pp. 3802-8. doi:10.1245/s10434-013-3096-1.
Molin MD, et al. Clinicopathological Correlates of Activating GNAS Mutations in Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas. Ann Surg Oncol. 2013;20(12):3802-8. PubMed PMID: 23846778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. AU - Molin,Marco Dal, AU - Matthaei,Hanno, AU - Wu,Jian, AU - Blackford,Amanda, AU - Debeljak,Marija, AU - Rezaee,Neda, AU - Wolfgang,Christopher L, AU - Butturini,Giovanni, AU - Salvia,Roberto, AU - Bassi,Claudio, AU - Goggins,Michael G, AU - Kinzler,Kenneth W, AU - Vogelstein,Bert, AU - Eshleman,James R, AU - Hruban,Ralph H, AU - Maitra,Anirban, Y1 - 2013/07/12/ PY - 2013/03/27/received PY - 2013/7/13/entrez PY - 2013/7/13/pubmed PY - 2014/6/6/medline SP - 3802 EP - 8 JF - Annals of surgical oncology JO - Ann. Surg. Oncol. VL - 20 IS - 12 N2 - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are the most common cystic precursor lesions of invasive pancreatic cancer. The recent identification of activating GNAS mutations at codon 201 in IPMNs is a promising target for early detection and therapy. The purpose of this study was to explore clinicopathological correlates of GNAS mutational status in resected IPMNs. METHODS: Clinical and pathologic characteristics were retrieved on 54 patients in whom GNAS codon 201 mutational status was previously reported ("historical group", Wu et al. Sci Transl Med 3:92ra66, 2011). In addition, a separate cohort of 32 patients (validation group) was included. After microdissection and DNA extraction, GNAS status was determined in the validation group by pyrosequencing. RESULTS: GNAS activating mutations were found in 64% of the 32 IPMNs included in the validation group, compared with a previously reported prevalence of 57% in the historical group. Overall, 52 of 86 (61%) of IPMNs demonstrated GNAS mutations in the two studies combined. Analysis of both groups confirmed that demographic characteristics, tumor location, ductal system involvement, focality, size, grade of dysplasia, presence of an associated cancer, and overall survival were not correlated with GNAS mutational status. Stratified by histological subtype, 100% of intestinal type IPMNs demonstrated GNAS mutations compared to 51% of gastric IPMN, 71% of pancreatobiliary IPMNs, and 0% of oncocytic IPMNs. CONCLUSIONS: GNAS activating mutations can be reliably detected in IPMNs by pyrosequencing. In terms of clinicopathological parameters, only histological subtype was correlated with mutational frequency, with the intestinal phenotype always associated with GNAS mutations. SN - 1534-4681 UR - https://www.unboundmedicine.com/medline/citation/23846778/Clinicopathological_correlates_of_activating_GNAS_mutations_in_intraductal_papillary_mucinous_neoplasm__IPMN__of_the_pancreas_ L2 - https://dx.doi.org/10.1245/s10434-013-3096-1 DB - PRIME DP - Unbound Medicine ER -