在儿科高级神经胶质瘤中发现种系 PALB2 致病性变异.

PALB2 (BRCA2的合作伙伴和本地化) 基因编码共定位的蛋白质
使用BRCA2在核灶中，可能允许稳定的核内定位
BRCA2PALB2的积累在维持基因组完整性中通过其在其中的作用而起着至关重要的作用
Fanconi贫血和同源重组DNA修复途径. 它有
已知的功能丧失疾病机制. 双质PALB2致病变异已在常染色体隐性fanconi中描述
贫血. PALB2中的杂合致病变异与男性和雄性乳腺癌的风险增加有关
胰腺癌 (科学 324: 217; 癌症 71: 2222-2229; n engl j with with 371: 497-506). 在髓母细胞瘤患者中也观察到了杂合种系PALB2突变 (柳叶刀Oncol 19: 785-798). 然而, 尚未报道与PALB2相关的癌症对高度神经胶质瘤的易感性.
Here we report a germline PALB2 pathogenic variant (c.509_510delGA, p.Arg170Ilefs*14, NM_024675.3) found
in a pediatric patient with high-grade glioma. This variant was first
identified by tumor sequencing using the Children’s Hospital of
费城 (劈) Comprehensive Solid Tumor Panel and then confirmed to
be a germline change using the CHOP Comprehensive Hereditary Cancer Panel
on DNA from a blood sample of this patient. Parental studies showed that
this variant was paternally inherited. Further studies are needed to
illustrate if pathogenic variants in PALB2 convey increased risk to developing brain tumor. This case also highlights
the potential of identifying germline mutation through tumor sequencing.