Very Long-term Survival Following Resection for Pancreatic Cancer Is Not Explained by Commonly Mutated Genes: Results of Whole-Exome Sequencing Analysis
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Abstract
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 identified 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 identified 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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Long-term survivors and general patients did not show significant differences in their mutation profiles.
“Also, long-term survivors and general patients did not show significant differences in their mutation profiles 203.”
From Artificial intelligence in pancreatic cancer (2022) · cites this paper as [203]
Stage-matched PDAC long-term survivors do not show significant genomic differences compared with shorter-survival patients.
“analysis of stage-matched PDAC long term survivors has not demonstrated significant genomic differences compared to those patients with shorter survival”
From Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes (2019) · cites this paper as Dal Molin et al., 2015
A small subset of PDAC patients survive more than 5 years after surgery.
“a minor subset of patients survive more than 5-years post-surgery”
From Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes (2019) · cites this paper as Dal Molin et al., 2015
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“Also, long-term survivors and general patients did not show significant differences in their mutation profiles [203].”
BackgroundWhy is pancreatic cancer so deadly? The pathologist's view
Hruban, R. H., Gaida, M. M., Thompson, E., Hong, S., Noë, M., Brosens, L. A., Jongepier, M., Offerhaus, G. J. A., & Wood, L. D. (2019) · The Journal of Pathology · doi:10.1002/path.5260 · Cited by 115 · see citing works
Self-citation
- Authors
- Dal Molin, M., Zhang, M., de Wilde, R. F., Ottenhof, N. A., Rezaee, N., Wolfgang, C. L., Blackford, A., Vogelstein, B., Kinzler, K. W., Papadopoulos, N., Hruban, R. H., Maitra, A., & Wood, L. D.
- Affiliations
- 1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
- Johns Hopkins University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Wood, Laura D.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2015-04-14
- Volume
- 21
- Issue
- 8
- Pages
- 1944-1950
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4401626
- OpenAlex
- W2117315259
- Cited by
- 101
- References
- 40
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 13 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 7 · 2017: 13 · 2016: 6 · 2015: 7
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R37CA043460, P50CA062924, CA 62924)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- pancreatic ductal adenocarcinoma, pancreatic cancer surgery, somatic mutations, KRAS mutation, TP53, SMAD4, CDKN2A, RNF43, prognostic factors, tumor stage, surgical margins, tumor grade
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Pancreatic Neoplasms, Prognosis, Case-Control Studies, Carcinoma, Pancreatic Ductal, Tumor Burden, High-Throughput Nucleotide Sequencing, Exome, Mutation Rate, Neoplasm Grading
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