Genome-wide analysis of high-risk primary brain cancer pedigrees identifies PDXDC1 as a candidate brain cancer predisposition gene
Genome-wide analysis of high-risk primary brain cancer pedigrees identifies PDXDC1 as a candidate brain cancer predisposition gene
复制标题
DOI：
10.1093/neuonc/noaa161
复制
发表时间：
2021-02-01
期刊：
影响因子：
15.9
通讯作者：
Blumenthal, Deborah T.
中科院分区：
文献类型：
--
作者：
Cannon-Albright, Lisa A.;Farnham, James M.;Blumenthal, Deborah T.
背景有证据表明原发性脑癌的遗传因素。高风险脑癌家系的连锁分析已经确定了脑癌易感基因可能存在的候选区域。全基因组连锁分析是在一个独特的一组11个信息丰富的，扩展的，高风险的原发性脑癌家系中确定的人口家谱数据库，其中包括从2至6个抽样，相关的原发性脑癌病例。福尔马林固定石蜡包埋的组织样本保存在生物储存库中，允许分析扩展的家系。个别高风险家系是单一的信息在多个地区的连锁。在第2、3、14和16号染色体上观察到连锁的暗示性证据。特别是16号染色体区域包含一个有希望的候选基因，吡哆醛依赖性脱羧酶结构域1（PDXDC 1），与先前的证据参与胶质母细胞瘤从其他先前报道的实验设置，并包含铅单核苷酸多态性（rs3198697）从16号染色体区域的连锁分析。在代表同质犹他州人群的独特家谱资源中，已经确定了原发性脑癌统计过量的家系。这些家系的全基因组连锁分析已经确定了一个潜在的候选易感基因，以及多个候选区域，可能窝藏易感基因座，并建议进一步分析。
Background. There is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside.Methods. Genome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Access to formalin-fixed paraffin embedded tissue samples archived in a biorepository allowed analysis of extended pedigrees.Results. Individual high-risk pedigrees were singly informative for linkage at multiple regions. Suggestive evidence for linkage was observed on chromosomes 2, 3, 14, and 16. The chromosome 16 region in particular contains a promising candidate gene, pyridoxal-dependent decarboxylase domain-containing 1 (PDXDC1), with prior evidence for involvement with glioblastoma from other previously reported experimental settings, and contains the lead single nucleotide polymorphism (rs3198697) from the linkage analysis of the chromosome 16 region.Conclusions. Pedigrees with a statistical excess of primary brain cancers have been identified in a unique genealogy resource representing the homogeneous Utah population. Genome-wide linkage analysis of these pedigrees has identified a potential candidate predisposition gene, as well as multiple candidate regions that could harbor predisposition loci, and for which further analysis is suggested.