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Molecular classification of familial non-BRCA1/BRCA2 breast cancer

Hedenfalk, Ingrid LU ; Ringnér, Markus LU ; Ben-Dor, Amir; Yakhini, Zohar; Chen, Yidong; Chebil, Gunilla; Ach, R; Loman, Niklas LU ; Olsson, Håkan LU and Meltzer, Paul, et al. (2003) In Proceedings of the National Academy of Sciences 100(5). p.2532-2537
Abstract
In the decade since their discovery, the two major breast cancer susceptibility genes BRCA1 and BRCA2, have been shown conclusively to be involved in a significant fraction of families segregating breast and ovarian cancer. However, it has become equally clear that a large proportion of families segregating breast cancer alone are not caused by mutations in BRCA1 or BRCA2. Unfortunately, despite intensive effort, the identification of additional breast cancer predisposition genes has so far been unsuccessful, presumably because of genetic heterogeneity, low penetrance, or recessive/polygenic mechanisms. These non-BRCA1/2 breast cancer families (termed BRCAx families) comprise a histopathologically heterogeneous group, further supporting... (More)
In the decade since their discovery, the two major breast cancer susceptibility genes BRCA1 and BRCA2, have been shown conclusively to be involved in a significant fraction of families segregating breast and ovarian cancer. However, it has become equally clear that a large proportion of families segregating breast cancer alone are not caused by mutations in BRCA1 or BRCA2. Unfortunately, despite intensive effort, the identification of additional breast cancer predisposition genes has so far been unsuccessful, presumably because of genetic heterogeneity, low penetrance, or recessive/polygenic mechanisms. These non-BRCA1/2 breast cancer families (termed BRCAx families) comprise a histopathologically heterogeneous group, further supporting their origin from multiple genetic events. Accordingly, the identification of a method to successfully subdivide BRCAx families into recognizable groups could be of considerable value to further genetic analysis. We have previously shown that global gene expression analysis can identify unique and distinct expression profiles in breast tumors from BRCA1 and BRCA2 mutation carriers. Here we show that gene expression profiling can discover novel classes among BRCAx tumors, and differentiate them from BRCA1 and BRCA2 tumors. Moreover, microarray-based comparative genomic hybridization (CGH) to cDNA arrays revealed specific somatic genetic alterations within the BRCAx subgroups. These findings illustrate that, when gene expression-based classifications are used, BRCAx families can be grouped into homogeneous subsets, thereby potentially increasing the power of conventional genetic analysis. (Less)
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Proceedings of the National Academy of Sciences
volume
100
issue
5
pages
2532 - 2537
publisher
National Acad Sciences
external identifiers
  • wos:000181365000067
  • pmid:12610208
  • scopus:0037418232
ISSN
1091-6490
DOI
10.1073/pnas.0533805100
language
English
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aaaf3fbd-2fb8-40cd-91ae-8f72a0042fa3 (old id 317173)
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2007-09-13 07:46:41
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2018-01-14 03:22:13
@article{aaaf3fbd-2fb8-40cd-91ae-8f72a0042fa3,
  abstract     = {In the decade since their discovery, the two major breast cancer susceptibility genes BRCA1 and BRCA2, have been shown conclusively to be involved in a significant fraction of families segregating breast and ovarian cancer. However, it has become equally clear that a large proportion of families segregating breast cancer alone are not caused by mutations in BRCA1 or BRCA2. Unfortunately, despite intensive effort, the identification of additional breast cancer predisposition genes has so far been unsuccessful, presumably because of genetic heterogeneity, low penetrance, or recessive/polygenic mechanisms. These non-BRCA1/2 breast cancer families (termed BRCAx families) comprise a histopathologically heterogeneous group, further supporting their origin from multiple genetic events. Accordingly, the identification of a method to successfully subdivide BRCAx families into recognizable groups could be of considerable value to further genetic analysis. We have previously shown that global gene expression analysis can identify unique and distinct expression profiles in breast tumors from BRCA1 and BRCA2 mutation carriers. Here we show that gene expression profiling can discover novel classes among BRCAx tumors, and differentiate them from BRCA1 and BRCA2 tumors. Moreover, microarray-based comparative genomic hybridization (CGH) to cDNA arrays revealed specific somatic genetic alterations within the BRCAx subgroups. These findings illustrate that, when gene expression-based classifications are used, BRCAx families can be grouped into homogeneous subsets, thereby potentially increasing the power of conventional genetic analysis.},
  author       = {Hedenfalk, Ingrid and Ringnér, Markus and Ben-Dor, Amir and Yakhini, Zohar and Chen, Yidong and Chebil, Gunilla and Ach, R and Loman, Niklas and Olsson, Håkan and Meltzer, Paul and Borg, Åke and Trent, Jeffrey},
  issn         = {1091-6490},
  language     = {eng},
  number       = {5},
  pages        = {2532--2537},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Molecular classification of familial non-BRCA1/BRCA2 breast cancer},
  url          = {http://dx.doi.org/10.1073/pnas.0533805100},
  volume       = {100},
  year         = {2003},
}