Tischkowitz Marc, Sabbaghian Nelly, Ray Anna M, Lange Ethan M, Foulkes William D, Cooney Kathleen A
Program in Cancer Genetics, Department of Oncology, McGill University, Montréal, QC, Canada.
Prostate. 2008 May 1;68(6):675-8. doi: 10.1002/pros.20729.
The genetic basis of susceptibility to prostate cancer (PRCA) remains elusive. Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases. PALB2 is a recently identified breast cancer susceptibility gene whose protein is closely associated with BRCA2 and is essential for BRCA2 anchorage to nuclear structures. This functional relationship made PALB2 a candidate PRCA susceptibility gene.
We sequenced PALB2 in probands from 95 PRCA families, 77 of which had two or more cases of early onset PRCA (age at diagnosis <55 years), and the remaining 18 had one case of early onset PRCA and five or more total cases of PRCA.
Two previously unreported variants, K18R and V925L were identified, neither of which is in a known PALB2 functional domain and both of which are unlikely to be pathogenic. No truncating mutations were identified.
These results indicate that deleterious PALB2 mutations are unlikely to play a significant role in hereditary prostate cancer.
前列腺癌（PRCA）易感性的遗传基础仍不清楚。BRCA2突变与前列腺癌风险增加相关，约占年轻发病（<56岁）前列腺癌病例的2%。PALB2是最近发现的乳腺癌易感基因，其蛋白质与BRCA2密切相关，对BRCA2锚定到核结构至关重要。这种功能关系使PALB2成为PRCA易感基因的候选者。
我们对来自95个PRCA家族的先证者进行了PALB2测序，其中77个家族有两例或更多例早发性PRCA（诊断年龄<55岁），其余18个家族有一例早发性PRCA和总共五例或更多例PRCA。
鉴定出两个以前未报道的变体，K18R和V925L，它们均不在已知的PALB2功能域中，且两者都不太可能是致病性的。未鉴定出截短突变。
这些结果表明，有害的PALB2突变不太可能在遗传性前列腺癌中起重要作用。
