دورية أكاديمية
High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers
| العنوان: | High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers |
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| المؤلفون: | Castro, E., Jugurnauth-Little, S., Karlsson, Q., Al-Shahrour, F., Pineiro-Yanez, E., Van de Poll, F., Leongamornlert, D., Dadaev, T., Govindasami, K., Guy, M., Eeles, R., Kote-Jarai, Z. |
| المصدر: | Castro , E , Jugurnauth-Little , S , Karlsson , Q , Al-Shahrour , F , Pineiro-Yanez , E , Van de Poll , F , Leongamornlert , D , Dadaev , T , Govindasami , K , Guy , M , Eeles , R , Kote-Jarai , Z , UKGPCS Study , EMBRACE Study & IMPACT Study 2015 , ' High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers ' , Annals of Oncology , vol. 26 , no. 11 , pp. 2293-2300 . https://doi.org/10.1093/annonc/mdv356Test |
| سنة النشر: | 2015 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | prostate cancer, germline, BRCA2, CNV, c-MYC, LOH, COMPARATIVE GENOMIC HYBRIDIZATION, EPITHELIAL OVARIAN-CANCER, BRCANESS, RELAPSE, HETEROZYGOSITY, SUSCEPTIBILITY, PROGRESSION, EXPRESSION, SURVIVAL, LOCUS |
| الوصف: | Background: Germline BRCA2 mutations are associated with poorer outcome prostate cancer ( PCa) compared with sporadic tumours but this association remains to be characterised. In this study, we aim to assess if there is a signature set of copy number alterations ( CNA) that could aid to the identification of BRCA2- mutated tumours and would assist us to understand their aggressive clinical behaviour. Methods: High- resolution array comparative genomic hybridisation profiling of DNA from PCa and matched morphologically normal prostate samples from 9 BRCA2 germline mutation carriers and 16 non- carriers in combination with unsupervised analysis was used to define copy number features. Results: PCa from BRCA2 germline mutation carriers ( B2T) harbour significantly more CNA than non- carrier tumours ( NCTs) ( P = 14 x 10(-6)). A hundred and sixteen regions had a significantly different distribution with both false discovery rate ( FDR) and P value <0.01, including CNA in the genomic region containing c- MYC that was present in 89% B2T versus 12.5% NCT ( P = 3 x 10(-4)). Loss of heterozygosity ( LOH) at the BRCA2 locus was observed in 67% of B2T. Elevated CNA are already present in 50% of the morphologically normal prostate tissue from BRCA2 carriers. Conclusion: The relative high amount of CNAs in morphologically normal prostate tissue of BRCA2 carriers implies a field effect and together with the observed LOH could be used as a marker of PCa risk in these men. Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2- mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/bfd8fdbe-8213-4fdf-bfb4-84a1deaf7117Test |
| DOI: | 10.1093/annonc/mdv356 |
| الإتاحة: | https://doi.org/10.1093/annonc/mdv356Test https://hdl.handle.net/11370/bfd8fdbe-8213-4fdf-bfb4-84a1deaf7117Test https://research.rug.nl/en/publications/bfd8fdbe-8213-4fdf-bfb4-84a1deaf7117Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.613C5C3A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/annonc/mdv356 |
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