The Consensus Coding Sequences of Human Breast and Colorectal Cancers

TLDR

The human genome sequence enables detailed identification of genetic alterations in cancers. The study aimed to systematically analyze genetic alterations by sequencing well‑annotated protein‑coding genes in breast and colorectal cancers. The authors sequenced 13,023 protein‑coding genes in 22 tumors and applied stringent criteria to identify 189 frequently mutated genes. Each tumor harbors about 90 mutant genes, yet only 189 (≈11 per tumor) are frequently mutated and likely drive cancer, many of which are novel and affect diverse cellular functions, offering new diagnostic and therapeutic targets.

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.