دورية أكاديمية
Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease
| العنوان: | Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease |
|---|---|
| المؤلفون: | Mijuskovic, M, Saunders, EJ, Leongamornlert, DA, Wakerell, S, Whitmore, I, Dadaev, T, Cieza-Borrella, C, Govindasami, K, Brook, MN, Haiman, CA, Conti, DV, Eeles, RA, Kote-Jarai, Z |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2018 |
| المجموعة: | St George's University of London: Repository |
| الوصف: | Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://openaccess.sgul.ac.uk/id/eprint/111859/1/41416_2018_Article_141.pdfTest; Mijuskovic, M; Saunders, EJ; Leongamornlert, DA; Wakerell, S; Whitmore, I; Dadaev, T; Cieza-Borrella, C; Govindasami, K; Brook, MN; Haiman, CA; et al. Mijuskovic, M; Saunders, EJ; Leongamornlert, DA; Wakerell, S; Whitmore, I; Dadaev, T; Cieza-Borrella, C; Govindasami, K; Brook, MN; Haiman, CA; Conti, DV; Eeles, RA; Kote-Jarai, Z (2018) Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease. British Journal of Cancer, 119 (1). pp. 96-104. ISSN 0007-0920 https://doi.org/10.1038/s41416-018-0141-7Test SGUL Authors: Cieza-Borrella, Clara Isabel |
| الإتاحة: | https://doi.org/10.1038/s41416-018-0141-7Test https://openaccess.sgul.ac.uk/id/eprint/111859Test/ https://openaccess.sgul.ac.uk/id/eprint/111859/1/41416_2018_Article_141.pdfTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.6F20535F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |