aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: Coordinate involvement of the regions including BCR and ABL

Abstract

In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene Another region spanning 22q11-13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome Coordinate 22q11-13 alterations were observed in nine of eleven tumors with the 9q34 alteration Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-31.3 were found associated with this instability only in tumors from patients with a smoking history Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas.

Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations

“…EGFR, encoding the epidermal growth factor receptor, was used as an intrachromosomal control to cover a centromeric locus on the p-arm. RPS6KC1 was chosen as a reference for gene dosage normalization: this gene is contained in the subtelomeric region of chromosome 1q, which is typically spared by events of chromosomal instability in colorectal cancer (22). A summary of the clinical characteristics for the study cohort can be found in Table 1 and detailed information is provided in Supplementary Table S2.…”

Biological and functional analysis of statistically significant pathways deregulated in colon cancer by using gene expression profiles

“…ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1; Location:9q34.1) proto-oncogene has been implicated in processes of cell differentiation, cell division, cell adhesion, death, and stress response. Several findings suggest that the 9q34 region was altered in some cases of sporadic colorectal carcinomas 39. The protein encoded by ATM (ataxia telangiectasia mutated; Location:11q22-q23) gene is an important cell cycle checkpoint kinase which functions as a regulator of a wide variety of downstream proteins.…”

Genetic and epigenetic heterogeneity in cancer: A genome‐centric perspective

“…For example, p53 is one of the most studied molecules and has the highest level of heterogeneity (Resnick et al, 2005;Rodier et al, 2007;Murray-Zmijewski et al, 2008;Whibley et al, 2009). (2) Increased usage of molecular cytogenetic methods (such as FISH detection) when coupled with laser micro-dissection can differentiate profiles of individual cells from the same tumor or can compare primary and metastatic tumors from the same patient (Fujii et al, 1996;Heng et al, 1997Heng et al, , 2004bKuukasjärvi et al, 1997;Aubele et al, 1999;Klein et al, 2002;Albertson et al, 2003;Bartos et al, 2007;Bayani et al, 2007). This type of analysis has clearly demonstrated that genome level alteration within tumors is a universal feature.…”