Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumors

Abstract

Identification of gene amplifications in human tumors is important for the understanding of tumorigenesis and may lead to discovery of diagnostic and prognostic markers. In this study, we used a microarray-based comparative genomic hybridization (CGH) technique, combined with conventional CGH, to identify gene amplifications in 43 tumors including eight pulmonary artery intimal sarcomas and 35 adrenocortical tumors. Conventional CGH revealed gains or amplifications of 12q13-q15 in six sarcomas and in two adrenocortical carcinomas. Using microarrays, we demonstrated that, among genes located on 12q13-q15, SAS/CDK4 were amplified in six sarcomas, and MDM2 and GLI in five and four sarcomas, respectively. The two adrenocortical tumors showed coamplifications of SAS/CDK4 and MDM2. Furthermore, PDGFRA (located on 4q12) amplification was identified in five sarcomas. Our data demonstrate: (1) amplifications of SAS/CDK4, MDM2, GLI, and PDGFRA are strongly associated with the tumorigenesis of pulmonary artery intimal sarcomas, whereas SAS/CDK4 and MDM2 coamplification may contribute to the progression of adrenocortical tumors; (2) microarray-based CGH is a useful tool for simultaneous detection of multiple gene amplifications, with a high sensitivity and resolution compared to that of conventional CGH.

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

“…Array CGH technology permits detection of specific genes with copy number variations, and it has been used to screen human solid cancers for genomic imbalances. [27][28][29][30][31][32][33][34] We also used a genomic DNA microarray to investigate DCNAs for 287 target clones in HCV-HCC; however, the number of DNA clones was very small. Array CGH detected DNA copy number alterations for the HRAS, THRA, TNFRSF6B/DCR3, FGR/SRC2, and GSCL genes, whereas conventional CGH did not always detect such changes.…”

Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

“…Characteristics of these gene sets are presented in Table 3. Cytogenetic (CGH and FISH) data on adrenocortical tumours were acquired from 10 publications found by literature search (Kjellman et al, 1996;Figueiredo et al, 1999Figueiredo et al, , 2005Russell et al, 1999;Zhao et al, 1999Zhao et al, , 2002Dohna et al, 2000;Sidhu et al, 2002;Bertherat et al, 2003;Stephan et al, 2008). These included 87 ACA and 124 ACC samples (Supplementary Table 3).…”

Tyrosine Kinases as Targets for Cancer Therapy

“…93 Imatinib is also active in dermatofibrosarcoma protuberans, 87 in which platelet-derived growth factor B is fused to collagen type I a 1 and overexpressed. 86 Finally, PDGFR a or PDGFR b is overexpressed in a subset of sarcomas 72,82,84 and chordomas, 94 some of which respond to imatinib (Table 2).…”