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Volume 11
Issue 12
10.3390/genes11121391
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Article

Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases

by
Viktor Hlavac
1,2,*,
Beatrice Mohelnikova-Duchonova
3,
Martin Lovecek
4,
Jiri Ehrmann
5,
Veronika Brynychova
1,2,
Katerina Kolarova
3 and
Pavel Soucek
1,2
1
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 306 05 Pilsen, Czech Republic
2
Toxicogenomics Unit, National Institute of Public Health, 100 42 Prague, Czech Republic
3
Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic
4
Department of Surgery I, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic
5
Department of Clinical and Molecular Pathology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic
*
Author to whom correspondence should be addressed.
Genes 2020, 11(12), 1391; https://doi.org/10.3390/genes11121391
Submission received: 15 October 2020 / Revised: 20 November 2020 / Accepted: 22 November 2020 / Published: 24 November 2020
(This article belongs to the Special Issue Personalized Diagnostic Tools and Methods to Assess Genetic Predisposition in Human Disease)
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Abstract

Mutation spectra of 250 cancer driver, druggable, and actionable genes were analyzed in surgically resected pancreatic ductal adenocarcinoma (PDAC) patients who developed metachronous pulmonary metastases. Targeted sequencing was performed in DNA from blood and archival samples of 15 primary tumors and three paired metastases. Results were complemented with the determination of G12V mutation in KRAS by droplet digital PCR. The median number of protein-changing mutations was 52 per patient. KRAS and TP53 were significantly enriched in fractions of mutations in hotspots. Individual gene mutation frequencies or mutational loads accounting separately for drivers, druggable, or clinically actionable genes, did not significantly associate with patients’ survival. LRP1B was markedly mutated in primaries of patients who generalized (71%) compared to those developing solitary pulmonary metastases (0%). FLG2 was mutated exclusively in primary tumors compared to paired metastases. In conclusion, signatures of prognostically differing subgroups of PDAC patients were generated for further utilization in precision medicine.
Keywords: pancreas; adenocarcinoma; next-generation sequencing; survival; pulmonary; metastases pancreas; adenocarcinoma; next-generation sequencing; survival; pulmonary; metastases

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MDPI and ACS Style

Hlavac, V.; Mohelnikova-Duchonova, B.; Lovecek, M.; Ehrmann, J.; Brynychova, V.; Kolarova, K.; Soucek, P. Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases. Genes 2020, 11, 1391. https://doi.org/10.3390/genes11121391

AMA Style

Hlavac V, Mohelnikova-Duchonova B, Lovecek M, Ehrmann J, Brynychova V, Kolarova K, Soucek P. Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases. Genes. 2020; 11(12):1391. https://doi.org/10.3390/genes11121391

Chicago/Turabian Style

Hlavac, Viktor, Beatrice Mohelnikova-Duchonova, Martin Lovecek, Jiri Ehrmann, Veronika Brynychova, Katerina Kolarova, and Pavel Soucek. 2020. "Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases" Genes 11, no. 12: 1391. https://doi.org/10.3390/genes11121391

APA Style

Hlavac, V., Mohelnikova-Duchonova, B., Lovecek, M., Ehrmann, J., Brynychova, V., Kolarova, K., & Soucek, P. (2020). Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases. Genes, 11(12), 1391. https://doi.org/10.3390/genes11121391

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