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 journalArticle

Abstract

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
Volume344
Issue number8
DOIs
StatePublished - Feb 22 2001
Externally publishedYes

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Transcriptome
Breast Neoplasms
Mutation
Neoplasms
Genes
Genotype
BRCA2 Gene
Analysis of Variance
Multivariate Analysis
Complementary DNA
Clone Cells
RNA
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hedenfalk, I., Duggan, D., Chen, Y., Radmacher, M., Bittner, M., Simon, R., ... Trent, J. (2001). Gene-expression profiles in hereditary breast cancer. New England Journal of Medicine, 344(8), 539-548. https://doi.org/10.1056/NEJM200102223440801

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

In: New England Journal of Medicine, Vol. 344, No. 8, 22.02.2001, p. 539-548.

Research output: Contribution to journalArticle

Hedenfalk, I, Duggan, D, Chen, Y, Radmacher, M, Bittner, M, Simon, R, Meltzer, P, Gusterson, B, Esteller, M, Raffeld, M, Yakhini, Z, Ben-Dor, A, Dougherty, E, Kononen, J, Bubendorf, L, Fehrle, W, Pittaluga, S, Gruvberger, S, Loman, N, Johannsson, O, Olsson, H, Wilfond, B, Sauter, G, Kallioniemi, OP, Borg, A & Trent, J 2001, 'Gene-expression profiles in hereditary breast cancer', New England Journal of Medicine, vol. 344, no. 8, pp. 539-548. https://doi.org/10.1056/NEJM200102223440801
Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R et al. Gene-expression profiles in hereditary breast cancer. New England Journal of Medicine. 2001 Feb 22;344(8):539-548. https://doi.org/10.1056/NEJM200102223440801
Hedenfalk, Ingrid ; Duggan, David ; Chen, Yidong ; Radmacher, Michael ; Bittner, Michael ; Simon, Richard ; Meltzer, Paul ; Gusterson, Barry ; Esteller, Manel ; Raffeld, Mark ; Yakhini, Zohar ; Ben-Dor, Amir ; Dougherty, Edward ; Kononen, Juha ; Bubendorf, Lukas ; Fehrle, Wilfrid ; Pittaluga, Stefania ; Gruvberger, Sofia ; Loman, Niklas ; Johannsson, Oskar ; Olsson, Håkan ; Wilfond, Benjamin ; Sauter, Guido ; Kallioniemi, Olli P. ; Borg, Ake ; Trent, Jeffrey. / Gene-expression profiles in hereditary breast cancer. In: New England Journal of Medicine. 2001 ; Vol. 344, No. 8. pp. 539-548.
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AU - Hedenfalk, Ingrid

AU - Duggan, David

AU - Chen, Yidong

AU - Radmacher, Michael

AU - Bittner, Michael

AU - Simon, Richard

AU - Meltzer, Paul

AU - Gusterson, Barry

AU - Esteller, Manel

AU - Raffeld, Mark

AU - Yakhini, Zohar

AU - Ben-Dor, Amir

AU - Dougherty, Edward

AU - Kononen, Juha

AU - Bubendorf, Lukas

AU - Fehrle, Wilfrid

AU - Pittaluga, Stefania

AU - Gruvberger, Sofia

AU - Loman, Niklas

AU - Johannsson, Oskar

AU - Olsson, Håkan

AU - Wilfond, Benjamin

AU - Sauter, Guido

AU - Kallioniemi, Olli P.

AU - Borg, Ake

AU - Trent, Jeffrey

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N2 - 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.

AB - 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.

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