Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 18;4(5):e000525.
doi: 10.1136/esmoopen-2019-000525. eCollection 2019.

Genetic mapping of pancreatic cancer by targeted next-generation sequencing in a cohort of patients managed with nab-paclitaxel-based chemotherapy or agents targeting the EGFR axis: a retrospective analysis of the Hellenic Cooperative Oncology Group (HeCOG)

Affiliations

Genetic mapping of pancreatic cancer by targeted next-generation sequencing in a cohort of patients managed with nab-paclitaxel-based chemotherapy or agents targeting the EGFR axis: a retrospective analysis of the Hellenic Cooperative Oncology Group (HeCOG)

George Zarkavelis et al. ESMO Open. .

Abstract

Pancreatic cancer is one of the most fatal malignancies ranking fourth among the leading causes of cancer death with diagnosis at late stages carrying a dismal prognosis. The aim of our retrospective study was to describe the nature and the incidence of gene mutations and genomic instability in advanced pancreatic adenocarcinomas of a Greek patient population fully annotated with clinicopathological data. We used a targeted next-generation sequencing (NGS) panel encompassing genes commonly mutated in pancreatic tumours in a patient population managed with either nab-paclitaxel regimens or targeted compounds modulating the epidermal growth factor receptor (EGFR)/AKT/mTOR axis. We identified KRAS, TP53, SMAD4 and CDKN2A as being the most prevalent mutations in the study population with the exception of an intriguingly lower incidence regarding KRAS mutants. Homologous recombination gene mutations were found to be mutually exclusive with CDKN2A mutations. The coexistence of both KRAS and TP53 mutation seems to adversely affect the outcome of the patients whether treated with targeted therapy against EGFR/Akt/mTOR axis or cytotoxic drugs. The poor prognosis observed, correlated to late presentation, specific molecular mutations and to high mutational load warrant prospective validating studies and research into the mechanistic pathophysiology of pancreatic tumours for more effective therapeutic targeting.

Keywords: EGFR; genetic mapping; mutations; nab-paclitaxel; pancreatic cancer.

PubMed Disclaimer

Conflict of interest statement

Competing interests: VKa: Advisory Board of Amgen, Pfizer, Novartis, BI, Lilly, Astellas, Genesis-Pharma and Janssen. ES: Advisory Board of Merck, MSD, Asta-Zeneca, Roche, Amgen and Genesis. GF: Advisory Board of Pfizer, Sanofi and Roche. Honoraria from Astra-Zeneca. GP: Advisory Role: Roche, Honoraria: Roche, Speaker bureau: Roche, Grants: Amgen.

Figures

Figure 1
Figure 1
Remark diagram.
Figure 2
Figure 2
Map showing the distribution of pathogenic mutations per gene per tumour.

References

    1. Ducreux M, Cuhna AS, Caramella C, et al. . Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26 Suppl 5(suppl 5):v56–68. 10.1093/annonc/mdv295 - DOI - PubMed
    1. Cancer Genome Atlas Research Network Electronic address aadhe, cancer genome atlas research N. integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 2017;32(2:185–203. - PMC - PubMed
    1. McGranahan N, Favero F, de Bruin EC, et al. . Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med 2015;7:283ra54 10.1126/scitranslmed.aaa1408 - DOI - PMC - PubMed
    1. Cicenas J, Kvederaviciute K, Meskinyte I, et al. . Kras, TP53, CDKN2A, Smad4, BRCA1, and BRCA2 mutations in pancreatic cancer. Cancers 2017;9:42 5 10.3390/cancers9050042 - DOI - PMC - PubMed
    1. Waddell N, Pajic M, Patch A-M, et al. . Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015;518:495–501. 10.1038/nature14169 - DOI - PMC - PubMed