Putative chromosomal deletions on 9p, 9q and 22q occur preferentially in malignant gastrointestinal stromal tumors

Abstract

To characterize the type of genetic alterations in gastrointestinal stromal tumors (GISTs), we performed a comprehensive allelotype study of 14 GISTs (2 benign, 7 borderline and 5 malignant) by polymerase-chain-reaction and loss-ofheterozygosity (PCR-LOH) analysis using 102 microsatellite markers, and compared the results with comparativegenomic-hybridization (CGH) analysis. Among the 38 evaluated chromosomal arms, 16 (42.1%) showed LOH in at least one patient. Most frequent LOH was observed at chromosome 14p and 14q (9/14, 64%) and this was demonstrated in all types of GISTs (50% in benign, 71% in borderline and 80% in malignant). Additional chromosomal deletions were found in several chromosomal arms. Among them, deletions on chromosomal arms of 22q (3/14, 21.4%), 9p (2/14, 14.3%) and 9q (2/14, 14.3%) were the most frequent, and were detected only in malignant GISTs both by PCR-LOH and by CGH analysis. Additionally, 2 malignant GISTs with LOH on 9p showed homozygous deletions in the restricted area of 9p by multiplex PCR-LOH analysis. Thus, several putative chromosomal changes were preferentially present in malignant GISTs but rare in benign and borderline GISTs. These findings suggest that accumulated chromosomal changes may contribute to the progression and/or malignant transformation of GISTs.

Gastrointestinal stromal tumors: what do we know now?

“…53,79,84 Chromosomal and Molecular Alterations During GIST Progression of GISTs demonstrate either monosomy of chromosome 14, or partial loss of 14q. 37,[85][86][87][88][89] Interestingly, these chromosome 14 abnormalities are observed in both KIT-mutant and PDGFRA-mutant GISTs. 37,43 Deletions of 14q11.2 include the genes PARP2, APEX1, and NDRG2, whereas deletions of 14q32 include the SIVA gene.…”

“…37,43,85,86,89,91 Losses on chromosomes 1p, 9p, 11p, and 17p are successively less common than 14q and 22q losses, but are more significantly associated with malignancy ( Figure 4). 37,43,85,89,[91][92][93][94] Losses on chromosomes 10, 13q, and 15q have also been reported in GISTs. 43,91 Gains on chromosomes 8q (including MYC), 3q (including SMARCA3), and 17q are associated with metastatic behavior.…”

A molecular portrait of gastrointestinal stromal tumors: an integrative analysis of gene expression profiling and high-resolution genomic copy number

“…These chromosomal losses may represent an underlying pathogenetic event resulting in the inactivation or haploinsufficiency of tumor suppressor genes. [8][9][10][11][12][13][14][15][16][17][18][19][20] However, the biologic significance of these genetic alterations, as well as their clinical implications, remains unknown. To address this issue, we performed an integrative analysis of gene expression profiling and high-resolution genomic copy number in 25 GIST samples to investigate the relationship between karyotype and gene expression profile, and to identify new haploinsufficient tumor suppressor genes involved in GIST pathogenesis and tumor progression.…”

NF2 Expression Levels of Gastrointestinal Stromal Tumors: A Quantitative Real-Time PCR Study

“…Homozygous deletions were found in 2 GIST cases in the restricted area of 9p containing the CDKN2A gene 34 . Since homozygous deletion is one of the known mechanisms for inactivation of a tumor suppressor gene, it may be possible that inactivation of CDKN2A plays a role in tumorigenesis of GIST, at least in some cases.…”

“…The C-terminus of merlin is unique and lacks the conventional actin-binding region of the ERM proteins but it interacts with Factin through the N-terminus 5,9,[11][12][13][14] .…”