Genomics

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Array CGH Analysis in primary gastrointestinal stromal tumors


ABSTRACT: Gastrointestinal stromal tumors (GISTs) comprise a biologically diverse group of neoplasms with respect to activating mutations in either KIT or PDGFRA genes, histology, anatomic site of origin, and clinical aggressiveness. In this study, we applied the high resolution array-based comparative genomic hybridization (array-CGH) technology to 66 primary GISTs (40 gastric and 26 non-gastric, 48 with KIT- and 18 with PDGFRA-mutations) for identification of novel high-level alterations and for characterization of genotype-related genomic changes. All cases had genomic imbalances with the highest occurrence of chromosome 14q (73%), 1p (62%), 22q (59%), 15q (38%) and 13q (29%) losses. Our data indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of tumor genotype. Furthermore, DNA copy number changes showed a site dependent pattern. These included lower incidence of losses at 14q (87% vs. 35%), and higher frequency of losses at 1p (45%, vs. 85%) and 15q (17% vs. 69%) in non-gastric versus gastric site (p<0.001 for all). However, in the multivariate analysis with adjustment to tumor risk stratification, only the chromosome 14q loss site-dependent pattern of distribution retained its significance. These findings suggest that loss of chromosome 14q is a relatively late genetic event in the development of non-gastric GISTs, the lack of which is most likely substituted by the accumulation of chromosomes 1p/15q and other changes. The novel minimal overlapping regions of deletion at chromosome 1p (1p36.32-1p35.2, 1p34.1, and 1p22.1-1p21.3), 13q (13q14.11-q14.2 and 13q32.3-q33.1) and 15q23 were delineated, which point to chromosomal regions that may harbor genes relevant to the development of these neoplasms. Keywords: comparative genomic hybridization, genotype, site dependent changes

ORGANISM(S): Homo sapiens

PROVIDER: GSE5336 | GEO | 2006/11/08

SECONDARY ACCESSION(S): PRJNA96355

REPOSITORIES: GEO

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