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Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis
In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785368/ https://www.ncbi.nlm.nih.gov/pubmed/26961069 http://dx.doi.org/10.1038/srep22982 |
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author | Bria, E. Pilotto, S. Simbolo, M. Fassan, M. de Manzoni, G. Carbognin, L. Sperduti, I. Brunelli, M. Cataldo, I. Tomezzoli, A. Mafficini, A. Turri, G. Karachaliou, N. Rosell, R. Tortora, G. Scarpa, A. |
author_facet | Bria, E. Pilotto, S. Simbolo, M. Fassan, M. de Manzoni, G. Carbognin, L. Sperduti, I. Brunelli, M. Cataldo, I. Tomezzoli, A. Mafficini, A. Turri, G. Karachaliou, N. Rosell, R. Tortora, G. Scarpa, A. |
author_sort | Bria, E. |
collection | PubMed |
description | In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC. |
format | Online Article Text |
id | pubmed-4785368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47853682016-03-11 Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis Bria, E. Pilotto, S. Simbolo, M. Fassan, M. de Manzoni, G. Carbognin, L. Sperduti, I. Brunelli, M. Cataldo, I. Tomezzoli, A. Mafficini, A. Turri, G. Karachaliou, N. Rosell, R. Tortora, G. Scarpa, A. Sci Rep Article In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC. Nature Publishing Group 2016-03-10 /pmc/articles/PMC4785368/ /pubmed/26961069 http://dx.doi.org/10.1038/srep22982 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Bria, E. Pilotto, S. Simbolo, M. Fassan, M. de Manzoni, G. Carbognin, L. Sperduti, I. Brunelli, M. Cataldo, I. Tomezzoli, A. Mafficini, A. Turri, G. Karachaliou, N. Rosell, R. Tortora, G. Scarpa, A. Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
title | Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
title_full | Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
title_fullStr | Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
title_full_unstemmed | Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
title_short | Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
title_sort | comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785368/ https://www.ncbi.nlm.nih.gov/pubmed/26961069 http://dx.doi.org/10.1038/srep22982 |
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