Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients
Jazyk angličtina Země Dánsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26822949
DOI
10.1111/cge.12748
Knihovny.cz E-zdroje
- Klíčová slova
- DNA repair, FANCL, SOLiD next-generation sequencing, genetic predisposition testing, hereditary breast cancer, high-throughput nucleotide sequencing, sequencing panel,
- MeSH
- jaderné proteiny genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory prsu genetika MeSH
- oprava DNA genetika MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- protein FANCL genetika MeSH
- protein FANCN MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BRCA1 protein, human MeSH Prohlížeč
- BRCA2 protein, human MeSH Prohlížeč
- FANCL protein, human MeSH Prohlížeč
- jaderné proteiny MeSH
- nádorové supresorové proteiny MeSH
- PALB2 protein, human MeSH Prohlížeč
- protein BRCA1 MeSH
- protein BRCA2 MeSH
- protein FANCL MeSH
- protein FANCN MeSH
Hereditary breast cancer comprises a minor but clinically meaningful breast cancer (BC) subgroup. Mutations in the major BC-susceptibility genes are important prognostic and predictive markers; however, their carriers represent only 25% of high-risk BC patients. To further characterize variants influencing BC risk, we performed SOLiD sequencing of 581 genes in 325 BC patients (negatively tested in previous BRCA1/BRCA2/PALB2 analyses). In 105 (32%) patients, we identified and confirmed 127 truncating variants (89 unique; nonsense, frameshift indels, and splice site), 19 patients harbored more than one truncation. Forty-six (36 unique) truncating variants in 25 DNA repair genes were found in 41 (12%) patients, including 16 variants in the Fanconi anemia (FA) genes. The most frequent variant in FA genes was c.1096_1099dupATTA in FANCL that also show a borderline association with increased BC risk in subsequent analysis of enlarged groups of BC patients and controls. Another 81 (53 unique) truncating variants were identified in 48 non-DNA repair genes in 74 patients (23%) including 16 patients carrying variants in genes coding proteins of estrogen metabolism/signaling. Our results highlight the importance of mutations in the FA genes' family, and indicate that estrogen metabolism genes may reveal a novel candidate genetic component for BC susceptibility.
Citace poskytuje Crossref.org
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