Gene-expression profiles in hereditary breast cancer.

Background: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that t he genes expressed by these two types of tumors are also distinctive, perha ps allowing us to identify cases of hereditary breast cancer on the basis o f gene-expression profiles. Methods: RNA from samples of primary tumors from seven carriers of the BRCA 1 mutation, seven carriers of the BRCA2 mutation, and seven patients with s poradic cases of breast cancer was compared with a microarray of 6512 compl ementary DNA clones of 5361 genes. Statistical analyses were used to identi fy a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. Results: Permutation analysis of multivariate classification functions esta blished that the gene-expression profiles of tumors with BRCA1 mutations, t umors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differential ly expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations . Given the known properties of some of the genes in this panel, our findin gs indicate that there are functional differences between breast tumors wit h BRCA1 mutations and those with BRCA2 mutations. Conclusions: Significantly different groups of genes are expressed by breas t cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression p rofile of the cancer. (N Engl J Med 2001;344:539-48.) Copyright (C) 2001 Ma ssachusetts Medical Society.