Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
| العنوان: | Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer |
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| المؤلفون: | Dominic P. Williams, Thanh Tran, Mark S. Carey, Diana Iliev, Lisa M. Fitzgerald, Thomas C. Krivak, Jian Chen, Bryan T. Hennessy, Jennifer Potter, Karen Smith-McCune, Karen H. Lu, Victor Abkevich, Kirsten Timms, Jerry S. Lanchbury, Julie A. DeLoia, Srikanth Jammulapati, Alexander Gutin, Gordon B. Mills, Larissa A. Meyer, Russell Broaddus |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Adult, Cancer Research, endocrine system diseases, Colorectal cancer, Loss of Heterozygosity, Carcinoma, Ovarian Epithelial, Biology, Genetics & Genomics, Disease-Free Survival, Cohort Studies, Loss of heterozygosity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, DNA Breaks, Double-Stranded, Neoplasms, Glandular and Epithelial, skin and connective tissue diseases, Rucaparib, Aged, 030304 developmental biology, Aged, 80 and over, BRCA2 Protein, Ovarian Neoplasms, Genetics, 0303 health sciences, Oncogene, BRCA1 Protein, Recombinational DNA Repair, DNA double-strand break repair, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, DNA-Binding Proteins, ovarian cancer, Oncology, chemistry, homologous recombination deficiency, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Female, Homologous recombination, Ovarian cancer |
| الوصف: | Background: Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH). Methods: Ovarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. Results: Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10−11). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10−5 and 10−29), and identified breast and pancreatic cell lines with BRCA defects. Conclusion: The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers. |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::059442be3171a32c64b42aa57246d6b2 https://doi.org/10.1038/bjc.2012.451 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....059442be3171a32c64b42aa57246d6b2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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