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Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases

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...

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Autores principales: Hlavac, Viktor, Mohelnikova-Duchonova, Beatrice, Lovecek, Martin, Ehrmann, Jiri, Brynychova, Veronika, Kolarova, Katerina, Soucek, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760784/
https://www.ncbi.nlm.nih.gov/pubmed/33255265
http://dx.doi.org/10.3390/genes11121391
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author Hlavac, Viktor
Mohelnikova-Duchonova, Beatrice
Lovecek, Martin
Ehrmann, Jiri
Brynychova, Veronika
Kolarova, Katerina
Soucek, Pavel
author_facet Hlavac, Viktor
Mohelnikova-Duchonova, Beatrice
Lovecek, Martin
Ehrmann, Jiri
Brynychova, Veronika
Kolarova, Katerina
Soucek, Pavel
author_sort Hlavac, Viktor
collection PubMed
description 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.
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spelling pubmed-77607842020-12-26 Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases Hlavac, Viktor Mohelnikova-Duchonova, Beatrice Lovecek, Martin Ehrmann, Jiri Brynychova, Veronika Kolarova, Katerina Soucek, Pavel Genes (Basel) Article 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. MDPI 2020-11-24 /pmc/articles/PMC7760784/ /pubmed/33255265 http://dx.doi.org/10.3390/genes11121391 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hlavac, Viktor
Mohelnikova-Duchonova, Beatrice
Lovecek, Martin
Ehrmann, Jiri
Brynychova, Veronika
Kolarova, Katerina
Soucek, Pavel
Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases
title Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases
title_full Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases
title_fullStr Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases
title_full_unstemmed Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases
title_short Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases
title_sort targeted sequencing of pancreatic adenocarcinomas from patients with metachronous pulmonary metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760784/
https://www.ncbi.nlm.nih.gov/pubmed/33255265
http://dx.doi.org/10.3390/genes11121391
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