Lee Sulgi, Kambhampati Madhuri, Almira-Suarez M Isabel, Ho Cheng-Ying, Panditharatna Eshini, Berger Seth I, Turner Joyce, Van Mater David, Kilburn Lindsay, Packer Roger J, Myseros John S, Vilain Eric, Nazarian Javad, Bornhorst Miriam
Center for Genetic Medicine, Children's National Health System, Washington, DC, United States.
Institute for Biomedical Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Front Oncol. 2020 Jan 14;9:1507. doi: 10.3389/fonc.2019.01507. eCollection 2019.
Anaplastic astrocytomas are aggressive glial cancers that present poor prognosis and high recurrence. Heterozygous IDH1 R132H mutations are common in adolescent and young adult anaplastic astrocytomas. In a majority of cases, the IDH1 R132H mutation is unique to the tumor, although rare cases of anaplastic astrocytoma have been described in patients with mosaic IDH1 mutations (Ollier disease or Maffucci syndrome). Here, we present two siblings with IDH1 R132H mutant high grade astrocytomas diagnosed at 14 and 26 years of age. Analysis of IDH mutations in the siblings' tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells, and primary teeth indicate mosaicism of IDH. Whole exome sequencing of the tumor tissue did not reveal any other common mutations between the two siblings. This study demonstrates the first example of IDH1 R132H mosaicism, acquired during early development, that provides an alternative mechanism of cancer predisposition.
间变性星形细胞瘤是侵袭性神经胶质瘤，预后较差且复发率高。异柠檬酸脱氢酶1（IDH1）基因第132位密码子由精氨酸突变为组氨酸（R132H）的杂合突变在青少年和青年间变性星形细胞瘤中很常见。在大多数情况下，IDH1 R132H突变是肿瘤所特有的，尽管在患有IDH1基因镶嵌突变（Ollier病或Maffucci综合征）的患者中也有罕见的间变性星形细胞瘤病例报道。在此，我们报告了两名患有IDH1 R132H突变型高级别星形细胞瘤的兄弟姐妹，分别在14岁和26岁时被诊断出来。对这两名兄弟姐妹肿瘤组织及非肿瘤组织（包括脑健康区域、颊细胞和乳牙）中的IDH突变分析表明存在IDH基因镶嵌现象。对肿瘤组织进行的全外显子组测序未发现这两名兄弟姐妹之间存在任何其他共同突变。本研究证明了在早期发育过程中获得的IDH1 R132H基因镶嵌现象是癌症易感性的一种替代机制的首个实例。
