Gene-expression profiles in hereditary breast cancer

Ingrid Hedenfalk, David Duggan, Yidong Chen, Michael Radmacher, Michael Bittner, Richard Simon, Paul Meltzer, Barry Gusterson, Manel Esteller, Mark Raffeld, Zohar Yakhini, Amir Ben-Dor, Edward Dougherty, Juha Kononen, Lukas Bubendorf, Wilfrid Fehrle, Stefania Pittaluga, Sofia Gruvberger, Niklas Loman, Oskar JohannssonHåkan Olsson, Benjamin Wilfond, Guido Sauter, Olli P. Kallioniemi, Ake Borg, Jeffrey Trent

Research output: Contribution to journalArticlepeer-review

1415 Scopus citations


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 the genes expressed by these two types of tumors are also distinctive, perhaps allowing 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 sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. Results Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors 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 differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations. Conclusions Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.

Original languageEnglish (US)
Pages (from-to)539-548
Number of pages10
JournalNew England Journal of Medicine
Issue number8
StatePublished - Feb 22 2001
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Gene-expression profiles in hereditary breast cancer'. Together they form a unique fingerprint.

Cite this