室管膜下巨细胞星形细胞瘤(SEGA)是通常出现在门罗孔附近的一个或另一个侧脑室壁中的肿瘤,最常见的背景结节性硬化症(TSC)。TSC具有由TSC复合物亚基1或2(TSC1、TSC2)基因的种系突变引起的多种临床表现。没有TSC临床表现的SEGA被称为孤立的SEGA,假设是由仅肿瘤的TSC1/2突变引起的,或具有体细胞镶嵌突变的TSC的“形式”。然而,很难区分这两者。这里,我们报告了3例进行基因调查的单独SEGA患者,并回顾了这种罕见的表现。
两名患者完全切除SEGA,一名患者部分切除。通过DNA微阵列对肿瘤组织和外周血进行遗传分析,逆转录酶聚合酶链反应,和下一代测序与超深度测序的突变点。
所有3例患者的肿瘤均具有TSC2体细胞突变和杂合性缺失(LOH)。在一个病人中,在他的血液中1%的白细胞中也检测到相同的TSC2突变.肿瘤没有复发,在4年的随访期间,TSC的临床表现未出现.
孤立性SEGA的遗传原因可能是LOH的TSC2突变。在单独的SEGA患者中,马赛克突变可能存在于其他器官中,和TSC可能在以后的生活中临床表现;因此,患者应长期随访。
Subependymal giant cell astrocytomas (SEGAs) are tumors that usually arise in the wall of one or the other lateral ventricle near a foramen of Monro, most often on a background of tuberous sclerosis complex (TSC). TSC has a variety of clinical manifestations caused by germline mutations of the TSC complex subunit 1 or 2 (TSC1, TSC2) genes. SEGAs without clinical manifestations of TSC are termed solitary SEGAs, which are hypothesized to be caused by tumor-only TSC1/2 mutations, or \"forme fruste\" of TSC with somatic mosaic mutations. However, it is difficult to distinguish between the two. Here, we report three patients with genetically investigated solitary SEGAs and review this rare manifestation.
SEGA was completely removed in two patients and partially removed in one. Genetic analyses were performed on the tumor tissue and on peripheral blood via DNA microarray, reverse-transcriptase polymerase chain reaction, and next-generation sequencing with ultra-deep sequencing of mutation points.
All three patients had tumors with TSC2 somatic mutations and loss of heterozygosity (LOH). In one patient, the same TSC2 mutation was also detected in 1% of leukocytes in his blood. The tumors did not recur, and clinical manifestations of TSC did not develop during the 4-year follow-up.
The genetic cause of solitary SEGAs may be a TSC2 mutation with LOH. In patients with solitary SEGA, mosaic mutations may present in other organs, and TSC may clinically manifest later in life; therefore, patients should be followed up for prolonged periods.