The Genomic Landscapes of Human Breast and Colorectal Cancers

TLDR

Human cancer arises from the accumulation of mutations in oncogenes and tumor suppressor genes. The study aims to catalog genetic changes during tumorigenesis in breast and colorectal cancers and to describe statistical and bioinformatic tools that can identify mutations involved in tumorigenesis. The authors isolated DNA from 11 breast and 11 colorectal tumors, sequenced genes from the Reference Sequence database, and applied statistical and bioinformatic tools to analyze mutations. Analysis of 20,857 transcripts from 18,191 genes revealed that breast and colorectal cancers contain a few frequently mutated “mountain” genes and many low‑frequency “hill” mutations, highlighting cancer heterogeneity and informing personalized tumor diagnosis and therapy.

Abstract

Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.