Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity
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Ludmila Gorunova1, Kjetil Boye2,3, Ioannis Panagopoulos1, Jeanne-Marie Berner4, Bodil Bjerkehagen4,5,6, Ivar Hompland2, Ingvild Lobmaier4, Toto Hølmebakk2, Tarjei S. Hveem7, Sverre Heim1,5 and Francesca Micci1
1 Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
2 Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
3 Department of Tumor Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
4 Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
5 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
6 Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway
7 Section for Applied Informatics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
|Ludmila Gorunova,||email:||[email protected]|
|Francesca Micci,||email:||[email protected]|
Keywords: gastrointestinal stromal tumor; chromosome aberrations; intratumor heterogeneity;
Received: December 09, 2021 Accepted: February 17, 2022 Published: March 07, 2022
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.
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