Oncotarget

Research Papers:

Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity

Ludmila Gorunova _, Kjetil Boye, Ioannis Panagopoulos, Jeanne-Marie Berner, Bodil Bjerkehagen, Ivar Hompland, Ingvild Lobmaier, Toto Hølmebakk, Tarjei S. Hveem, Sverre Heim and Francesca Micci _

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Abstract

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

Correspondence to:

Ludmila Gorunova, email: ludmila.gorunova@ous-hf.no
Francesca Micci, email: francesca.micci@medisin.uio.no

Keywords: gastrointestinal stromal tumor; chromosome aberrations; intratumor heterogeneity; KIT mutations; PDGFRA mutations

Received: December 09, 2021     Accepted: February 17, 2022     Published: March 07, 2022

Copyright: © 2022 Gorunova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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