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Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity
Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm with variable behavior. An increased understanding of the tumor pathogenesis may improve clinical decision-making. Our aim was to obtain more data about the overall chromosome aberrations and intratumor cytogenetic heterogeneity in GIST...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901076/ https://www.ncbi.nlm.nih.gov/pubmed/35284037 http://dx.doi.org/10.18632/oncotarget.28209 |
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author | Gorunova, Ludmila Boye, Kjetil Panagopoulos, Ioannis Berner, Jeanne-Marie Bjerkehagen, Bodil Hompland, Ivar Lobmaier, Ingvild Hølmebakk, Toto Hveem, Tarjei S. Heim, Sverre Micci, Francesca |
author_facet | Gorunova, Ludmila Boye, Kjetil Panagopoulos, Ioannis Berner, Jeanne-Marie Bjerkehagen, Bodil Hompland, Ivar Lobmaier, Ingvild Hølmebakk, Toto Hveem, Tarjei S. Heim, Sverre Micci, Francesca |
author_sort | Gorunova, Ludmila |
collection | PubMed |
description | Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm with variable behavior. An increased understanding of the tumor pathogenesis may improve clinical decision-making. Our aim was to obtain more data about the overall chromosome aberrations and intratumor cytogenetic heterogeneity in GIST. We analyzed 306 GIST samples from 291 patients using G-banding, direct sequencing, and statistics. Clonal chromosome aberrations were found in 81% of samples, with 34% of 226 primary tumors demonstrating extensive cytogenetic heterogeneity. 135 tumors had simple (≤5 changes) and 91 had complex (>5 changes) karyotypes. The karyotypically complex tumors more often were non-gastric (P < 0.001), larger (P < 0.001), more mitotically active (P = 0.009) and had a higher risk of rupture (P < 0.001) and recurrence (P < 0.001). Significant differences between gastric and non-gastric tumors were found also in the frequency of main chromosome losses: of 14q (79% vs. 63%), 22q (38% vs. 67%), 1p (23% vs. 88%), and 15q (18% vs. 77%). Gastric PDGFRA-mutated tumors, compared with gastric KIT-mutated, had a lower incidence of 22q losses (18% vs. 43%) but a higher rate of 1p losses (42% vs. 22%). The present, largest by far karyotypic study of GISTs provides further evidence for the existence of variable pathogenetic pathways operating in these tumors’ development. |
format | Online Article Text |
id | pubmed-8901076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-89010762022-03-10 Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity Gorunova, Ludmila Boye, Kjetil Panagopoulos, Ioannis Berner, Jeanne-Marie Bjerkehagen, Bodil Hompland, Ivar Lobmaier, Ingvild Hølmebakk, Toto Hveem, Tarjei S. Heim, Sverre Micci, Francesca Oncotarget Research Paper Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm with variable behavior. An increased understanding of the tumor pathogenesis may improve clinical decision-making. Our aim was to obtain more data about the overall chromosome aberrations and intratumor cytogenetic heterogeneity in GIST. We analyzed 306 GIST samples from 291 patients using G-banding, direct sequencing, and statistics. Clonal chromosome aberrations were found in 81% of samples, with 34% of 226 primary tumors demonstrating extensive cytogenetic heterogeneity. 135 tumors had simple (≤5 changes) and 91 had complex (>5 changes) karyotypes. The karyotypically complex tumors more often were non-gastric (P < 0.001), larger (P < 0.001), more mitotically active (P = 0.009) and had a higher risk of rupture (P < 0.001) and recurrence (P < 0.001). Significant differences between gastric and non-gastric tumors were found also in the frequency of main chromosome losses: of 14q (79% vs. 63%), 22q (38% vs. 67%), 1p (23% vs. 88%), and 15q (18% vs. 77%). Gastric PDGFRA-mutated tumors, compared with gastric KIT-mutated, had a lower incidence of 22q losses (18% vs. 43%) but a higher rate of 1p losses (42% vs. 22%). The present, largest by far karyotypic study of GISTs provides further evidence for the existence of variable pathogenetic pathways operating in these tumors’ development. Impact Journals LLC 2022-03-07 /pmc/articles/PMC8901076/ /pubmed/35284037 http://dx.doi.org/10.18632/oncotarget.28209 Text en Copyright: © 2022 Gorunova et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gorunova, Ludmila Boye, Kjetil Panagopoulos, Ioannis Berner, Jeanne-Marie Bjerkehagen, Bodil Hompland, Ivar Lobmaier, Ingvild Hølmebakk, Toto Hveem, Tarjei S. Heim, Sverre Micci, Francesca Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
title | Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
title_full | Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
title_fullStr | Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
title_full_unstemmed | Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
title_short | Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
title_sort | cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901076/ https://www.ncbi.nlm.nih.gov/pubmed/35284037 http://dx.doi.org/10.18632/oncotarget.28209 |
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