Somatic Mutations in Exocrine Pancreatic Tumors: Association with Patient Survival
Open accessAbstract
KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application.
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CDKN2A aberrations, including point mutations and deletions, are found in 25% of tumors.
“CDKN2A aberrations, including point mutations and deletions, are found in 25% of tumors.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [52]
While CDKN2A aberrations alone do not significantly impact survival, concurrent mutations in both KRAS and CDKN2A are associated with the shortest survival, particularly in PDAC.
“While CDKN2A aberrations alone do not significantly impact survival, concurrent mutations in both KRAS and CDKN2A are associated with the shortest survival, particularly in PDAC [52].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [52]
Combination of KRAS and CDKN2A mutational status was proposed as potential independent prognostic marker.
“The combination of KRAS and CDKN2A mutational status was proposed as a potential independent prognostic marker [52].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [52]
KRAS mutations, particularly G12D variant, are associated with reduced median survival time.
“KRAS mutations, particularly the G12D variant, were associated with reduced median survival time.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [52]
The KRASG12D mutation was reported to be more immune suppressive with shorter survival in lung cancer and pancreatic cancer.
“The KRASG12D mutation was reported to be more immune suppressive with shorter survival in lung cancer and pancreatic cancer31,32.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [32]
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- Authors
- Rachakonda, P. S., Bauer, A. S., Xie, H., Campa, D., Rizzato, C., Canzian, F., Beghelli, S., Greenhalf, W., Costello, E., Schanne, M., Heller, A., Scarpa, A., Neoptolemos, J. P., Werner, J., Büchler, M., Hoheisel, J. D., Hemminki, K., Giese, N., & Kumar, R.
- Affiliations
- German Cancer Research Center (DE)
- University of Verona (IT)
- Cancer Research UK (GB)
- University Hospital Heidelberg (DE)
- Corresponding author
- Rachakonda, P. Sivaramakrishna
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-02
- Volume
- 8
- Issue
- 4
- Pages
- e60870
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3614935
- OpenAlex
- W1993147908
- Cited by
- 93
- References
- 36
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 14 · 2016: 11 · 2015: 12 · 2014: 8 · 2013: 1
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Pancreatic Cancer UK (2013 RIF)
- Cancer Research UK (15957)
- National Institute for Health and Care Research (NF-SI-0510-10126)
- Universität Heidelberg
- 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
- KRAS mutation, CDKN2A deletion, pancreatic ductal adenocarcinoma, exocrine pancreatic tumors, somatic mutations, patient survival, G12D mutation, codon 12, codon 61, prognostic factors
- MeSH terms
- Aged, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Proto-Oncogene Proteins, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), ras Proteins, Cyclin-Dependent Kinase Inhibitor p16, Kaplan-Meier Estimate
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