The Consensus Coding Sequences of Human Breast and Colorectal Cancers

Abstract

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of approximately 90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.

Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines

“…It is of interest that recent large-scale sequencing efforts have identified a similar number of somatic oncogenic mutations among breast cancers and colorectal cancers, but that the spectrum of mutated pathways was far more diverse among breast cancers (an average of 14 and 15 mutations per tumor among 108 and 38 pathways for breast cancer and colorectal cancer, respectively; [44,45]). These differences in mutation spectrum suggested genetic heterogeneity among breast cancers, and are thus in line with our finding of two distinct gene mutations profiles.…”

Reactivation of mutant p53: molecular mechanisms and therapeutic potential

“…The exceptionally high frequency of p53 mutations in human tumors of diverse types makes p53 unique among genes involved in tumor development (see p53.free.fr and www-p53.iarc.fr; Be´roud and Soussi, 1998;Olivier et al, 2002). Indeed, unbiased sequencing of whole genomes of breast and colon cancers confirmed that p53 is the most commonly mutated gene in these tumors (Sjo¨blom et al, 2006). Accordingly, p53 is the focus of research aimed at development of novel anticancer drugs.…”

Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk

“…TCF7L2 frameshift mutation in MSI-H CRC leads to selective loss of TCF7L2 isoforms with CtBPbinding abilities [4]. Recently, a genome-wide analysis of 11 CRC tumor cell lines or xenografts classified TCF7L2 [5] as a cancer candidate gene (with a cancer mutation prevalance, CaMP, score of 2.8; >1 is a cancer candidate gene). Polymorphisms in TCF7L2 have been associated with disease susceptibility.…”