Cox Devin M, Nelson Katherine L, Clytone Meera, Collins Debra L
University of Kansas Cancer Center, Westwood, Kansas.
Mol Genet Genomic Med. 2018 Nov;6(6):1236-1242. doi: 10.1002/mgg3.460. Epub 2018 Aug 27.
Historically, three founder mutations in the BRCA1/2 (OMIM 113705; OMIM 600185) genes have been the focus of cancer risks within the Ashkenazi Jewish (AJ) population. However, there are several additional mutations associated with increased susceptibility to cancer in individuals of AJ ancestry.
We report three patients who exemplify the need to keep these additional founder mutations in mind when pursuing hereditary cancer genetic testing of individuals in this population. All gene sequences in this paper were aligned to reference sequences based on human genome build GRCh37/UCSC hg19.
review of the literature discusses that the combined risk is 12.36%-20.83% forhaving 1 of the 10 hereditary cancer AJ founder mutations in the BRCA1, BRCA2, CHEK2 (OMIM 604373), APC (OMIM 611731), MSH2 (OMIM 609309), MSH6 (OMIM 600678), and GREM1 (OMIM 603054) genes for individuals of AJ ancestry.
We recommend testing for all 10 of these AJ founder cancer susceptibility mutations for individuals within this population as standard screening in order to ensure appropriate cancer risk management and cascade testing.
从历史上看，BRCA1/2（OMIM 113705；OMIM 600185）基因中的三种奠基者突变一直是阿什肯纳兹犹太（AJ）人群癌症风险的关注焦点。然而，在具有AJ血统的个体中，还有其他几种与癌症易感性增加相关的突变。
我们报告了三名患者，他们体现了在对该人群个体进行遗传性癌症基因检测时，需要牢记这些额外的奠基者突变。本文中的所有基因序列均根据人类基因组构建GRCh37/UCSC hg19与参考序列进行比对。
文献综述讨论了对于具有AJ血统的个体，在BRCA1、BRCA2、CHEK2（OMIM 604373）、APC（OMIM 611731）、MSH2（OMIM 609309）、MSH6（OMIM 600678）和GREM1（OMIM 603054）基因中，拥有10种遗传性癌症AJ奠基者突变之一的综合风险为12.36%-20.83%。
我们建议对该人群中的个体进行这10种AJ奠基者癌症易感性突变的全面检测，作为标准筛查，以确保适当的癌症风险管理和级联检测。
