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Gene-expression profiles in hereditary breast cancer

Hedenfalk, I LU ; Duggan, D; Chen, Y; Radmacher, M; Bittner, M; Simon, R; Meltzer, P; Gusterson, B; Esteller, M and Kallioniemi, O P, et al. (2001) In New England Journal of Medicine 344(8). p.48-539
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 tumor 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... (More)

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 tumor 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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keywords
Algorithms, BRCA2 Protein, Breast Neoplasms, DNA Methylation, DNA, Complementary, DNA, Neoplasm, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, BRCA1, Genotype, Germ-Line Mutation, Heterozygote, Humans, Neoplasm Proteins, Oligonucleotide Array Sequence Analysis, RNA, Messenger, RNA, Neoplasm, Transcription Factors
in
New England Journal of Medicine
volume
344
issue
8
pages
10 pages
publisher
Massachusetts Medical Society
external identifiers
  • pmid:11207349
  • wos:000167044600001
  • scopus:0035931947
ISSN
0028-4793
DOI
10.1056/NEJM200102223440801
language
English
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yes
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cbd27d05-bbd5-497a-bd34-5912b821a292 (old id 1120150)
date added to LUP
2008-06-30 13:05:35
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2018-04-08 03:34:13
@article{cbd27d05-bbd5-497a-bd34-5912b821a292,
  abstract     = {<p>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.</p><p>METHODS: RNA from samples of primary tumor 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.</p><p>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.</p><p>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.</p>},
  author       = {Hedenfalk, I and Duggan, D and Chen, Y and Radmacher, M and Bittner, M and Simon, R and Meltzer, P and Gusterson, B and Esteller, M and Kallioniemi, O P and Wilfond, B and Borg, Åke and Trent, J and Raffeld, M and Yakhini, Z and Ben-Dor, A and Dougherty, E and Kononen, J and Bubendorf, L and Fehrle, W and Pittaluga, S and Gruvberger, S and Loman, N and Johannsson, O and Olsson, Håkan and Sauter, G},
  issn         = {0028-4793},
  keyword      = {Algorithms,BRCA2 Protein,Breast Neoplasms,DNA Methylation,DNA, Complementary,DNA, Neoplasm,Gene Expression,Gene Expression Profiling,Gene Expression Regulation, Neoplastic,Genes, BRCA1,Genotype,Germ-Line Mutation,Heterozygote,Humans,Neoplasm Proteins,Oligonucleotide Array Sequence Analysis,RNA, Messenger,RNA, Neoplasm,Transcription Factors},
  language     = {eng},
  month        = {02},
  number       = {8},
  pages        = {48--539},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Gene-expression profiles in hereditary breast cancer},
  url          = {http://dx.doi.org/10.1056/NEJM200102223440801},
  volume       = {344},
  year         = {2001},
}