pap_Hedenfalk_2001

pap_Hedenfalk_2001 - T he New England Journal o f M edicine...

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The New England Journal of Medicine Copyright © 2001 by the Massachusetts Medical Society VOLUME 344 F EBRUARY 22, 2001 NUMBER 8 N Engl J Med, Vol. 344, No. 8 · February 22, 2001 · www.nejm.org · 539 GENE-EXPRESSION PROFILES IN HEREDITARY BREAST CANCER I NGRID H EDENFALK , M.S., D AVID D UGGAN , P H .D., Y IDONG C HEN , P H .D., M ICHAEL R ADMACHER , P H .D., M ICHAEL B ITTNER , P H .D., R ICHARD S IMON , D.S C ., P AUL M ELTZER , M.D., P H .D., B ARRY G USTERSON , M.D., P H .D., M ANEL E STELLER , M.D., P H .D., O LLI -P. K ALLIONIEMI , M.D., P H .D., B ENJAMIN W ILFOND , M.D., Å KE B ORG , P H .D., AND J EFFREY T RENT , P H .D. A BSTRACT Background Many cases of hereditary breast can- cer 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 the genes expressed by these two types of tumors are also distinctive, perhaps al- lowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles. Methods RNA from samples of primary tumors from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with spo- radic cases of breast cancer was compared with a mi- croarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 geno- type from the BRCA2 genotype. Results Permutation analysis of multivariate classi- fication functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed sig- nificantly from each other. An analysis of variance between the levels of gene expression and the gen- otype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 muta- tions and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differ- ences between breast tumors with BRCA1 mutations and those with BRCA2 mutations. Conclusions Significantly different groups of genes are expressed by breast cancers with BRCA1 muta- tions and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer. (N Engl J Med 2001;344:539-48.) Copyright © 2001 Massachusetts Medical Society. 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, Be- thesda, Md.; the Department of Oncology, University of Lund, Lund, Sweden (I.H., Å.B.); the Department of Pathology, Western Infirmary, Uni- versity of Glasgow, Glasgow, Scotland (B.G.); and the Division of Tumor Biology, Johns Hopkins Oncology Center, Baltimore (M.E.). Address re- print requests to Dr. Trent at the National Human Genome Research In- stitute, National Institutes of Health, Bldg. 49, Rm. 4A22, Bethesda, MD 20892-4470, or at jtrent@nih.gov.
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pap_Hedenfalk_2001 - T he New England Journal o f M edicine...

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