Background Many cases of hereditary breast cancer are due tomutations in either the BRCA1 or the BRCA2 gene. The histopathologicalchanges in these cancers are often characteristic of the mutantgene. We hypothesized that the genes expressed by these twotypes of tumors are also distinctive, perhaps allowing us toidentify cases of hereditary breast cancer on the basis of gene-expressionprofiles.
Methods RNA from samples of primary tumors from seven carriersof the BRCA1 mutation, seven carriers of the BRCA2 mutation,and seven patients with sporadic cases of breast cancer wascompared with a microarray of 6512 complementary DNA clonesof 5361 genes. Statistical analyses were used to identify aset of genes that could distinguish the BRCA1 genotype fromthe BRCA2 genotype.
Results Permutation analysis of multivariate classificationfunctions established that the gene-expression profiles of tumorswith BRCA1 mutations, tumors with BRCA2 mutations, and sporadictumors differed significantly from each other. An analysis ofvariance between the levels of gene expression and the genotypeof the samples identified 176 genes that were differentiallyexpressed in tumors with BRCA1 mutations and tumors with BRCA2mutations. Given the known properties of some of the genes inthis panel, our findings indicate that there are functionaldifferences between breast tumors with BRCA1 mutations and thosewith BRCA2 mutations.
Conclusions Significantly different groups of genes are expressedby breast cancers with BRCA1 mutations and breast cancers withBRCA2 mutations. Our results suggest that a heritable mutationinfluences the gene-expression profile of the cancer.
Source Information
From the Cancer Genetics Branch (I.H., D.D., Y.C., M.B., P.M., O.-P.K., J.T.) and the Medical Genetics Branch (B.W.), National Human Genome Research Institute, and the Division of Cancer Treatment and Diagnosis, National Cancer Institute (M.R., R.S.), National Institutes of Health, Bethesda, Md.; the Department of Oncology, University of Lund, Lund, Sweden (I.H., Å.B.); the Department of Pathology, Western Infirmary, University of Glasgow, Glasgow, Scotland (B.G.); and the Division of Tumor Biology, Johns Hopkins Oncology Center, Baltimore (M.E.).
Address reprint requests to Dr. Trent at the National Human Genome Research Institute, National Institutes of Health, Bldg. 49, Rm. 4A22, Bethesda, MD 20892-4470, or at jtrent{at}nih.gov.
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