Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers

Abstract

We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.amplification ͉ copy number changes ͉ Digital Karyotyping ͉ high-density SNP arrays ͉ homozygous deletion

A pathway-based classification of human breast cancer

“…Given that each of these phenotypic characteristics are the result of the expression of a unique complement of genes, the use of genome-scale gene expression analysis differs only in the scale of the data and the consequent ability to add greater precision to these determinations. Studies investigating genomic abnormalities and epigenetic modifications add complexity and detail to the description of cancer phenotypes (22)(23)(24). Although these data are important in describing cancer characteristics, it is critical to develop a unifying underlying platform that can accommodate complex data while concurrently reducing the complexity to a form that provides biological insight.…”

NTRK gene amplification in patients with metastatic cancer

“…Gene amplification, similar to gene mutation, plays a significant role in tumorigenesis in many types of cancer, such as gastric cancer, ovarian cancer, hepatocellular carcinoma, colon cancer, and others [22,23]. Thus, targeting the "driver genes" that are amplified may provide novel opportunities for precision medicine [20].…”

RNA Editing in RHOQ Promotes Invasion Potential in Colorectal Cancer

“…Genetic and epigenetic alterations, including chromosomal instability, microsatellite instability, and CpG island methylation, contribute to development and progression of CRC. Continuous efforts have been made to better understand the genomic signatures of CRC (Wood et al, 2007;Leary et al, 2008). Recently, comprehensive characterization of genomic alterations in CRC was made possible using next-generation sequencing technology (Bass et al, 2011;Seshagiri et al, 2012;Cancer Genome Atlas Network, 2012).…”