Abstract:
BACKGROUND:Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. METHODS:From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. RESULTS:The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. CONCLUSIONS:Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Rebbeck TR,Friebel TM,Mitra N,Wan F,Chen S,Andrulis IL,Apostolou P,Arnold N,Arun BK,Barrowdale D,Benitez J,Berger R,Berthet P,Borg A,Buys SS,Caldes T,Carter J,Chiquette J,Claes KB,Couch FJ,Cybulski C,Daly MB,ddoi
10.1186/s13058-016-0768-3subject
Has Abstractpub_date
2016-11-11 00:00:00pages
112issue
1eissn
1465-5411issn
1465-542Xpii
10.1186/s13058-016-0768-3journal_volume
18pub_type
杂志文章,多中心研究abstract::Therapeutic choices for metastatic tumors are, in most cases, based upon the histological and molecular analysis of the corresponding primary tumor. Understanding whether and to what extent the genomic landscape of metastasis differs from the tumors from which they originated is critical yet largely unknown. A recent ...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
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journal_title:Breast cancer research : BCR
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 评论,杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr1845
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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更新日期:2013-06-27 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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更新日期:2005-01-01 00:00:00
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更新日期:2003-01-01 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
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journal_title:Breast cancer research : BCR
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journal_title:Breast cancer research : BCR
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更新日期:2010-01-01 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,随机对照试验
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更新日期:2012-05-02 00:00:00