TY - JOUR
T1 - Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes
T2 - Results of whole-exome sequencing analysis
AU - Dal Molin, Marco
AU - Zhang, Ming
AU - De Wilde, Roeland F.
AU - Ottenhof, Niki A.
AU - Rezaee, Neda
AU - Wolfgang, Christopher L.
AU - Blackford, Amanda
AU - Vogelstein, Bert
AU - Kinzler, Kenneth W.
AU - Papadopoulos, Nickolas
AU - Hruban, Ralph H.
AU - Maitra, Anirban
AU - Wood, Laura D.
N1 - Publisher Copyright:
© 2015 AACR.
PY - 2015/4/15
Y1 - 2015/4/15
N2 - Purpose: The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTS). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival. Experimental Design: We sequenced the exomes of eight PDACs from patients who survived ≥10 years. On the basis of the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs. Results: KRAS mutations were identifi ed in 33 of 35 cancers (94%) from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identifi ed in four of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared with available data from PDACs unselected for survival. Comparison of clinicopathologic features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade, or nodal disease did not preclude long-term survival. Conclusions: Our results suggest that in most patients, somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC.
AB - Purpose: The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTS). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival. Experimental Design: We sequenced the exomes of eight PDACs from patients who survived ≥10 years. On the basis of the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs. Results: KRAS mutations were identifi ed in 33 of 35 cancers (94%) from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identifi ed in four of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared with available data from PDACs unselected for survival. Comparison of clinicopathologic features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade, or nodal disease did not preclude long-term survival. Conclusions: Our results suggest that in most patients, somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC.
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U2 - 10.1158/1078-0432.CCR-14-2600
DO - 10.1158/1078-0432.CCR-14-2600
M3 - Article
C2 - 25623214
AN - SCOPUS:84927583577
SN - 1078-0432
VL - 21
SP - 1944
EP - 1950
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -