Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Med Oncol. 2018 Mar 29;35(5):60. doi: 10.1007/s12032-018-1119-2.
According to the 2016 World Health Organization classification of tumors of the central nervous system, detecting 1p/19q co-deletion became essential in clinical neuropathology for gliomas with oligodendroglioma-like morphology. Here, we assessed genomic profiles of glioblastoma in 80 cases including 1p/19q status using fluorescent in situ hybridization (FISH), array-comparative genomic hybridization (aCGH), and/or whole exome sequencing (WES). Paraffin-embedded tumor tissues were subjected to FISH analysis, and the corresponding frozen tissues from the same tumors were evaluated for aCGH and/or WES for 1p/19q co-deletion and other genetic parameters, which included IDH1-R132H, ATRX, TP53, CIC, and NOTCH1 mutations and MGMT methylation status. We also evaluated correlations between 1p/19q co-deletion status and molecular markers or clinical outcomes. The FISH analyses revealed 1p/19q co-deletion in two cases, isolated deletion of 1p in six cases, and 19q in two cases, whereas the aCGH and WES results showed isolated deletion of 19q in four cases and 19 monosomy in only one case. Eleven cases showed discordant 1p/19q results between aCGH/WES and FISH analysis, and in most of them, 1p and/or 19q deletion on FISH analysis corresponded to the partial deletions at 1p36 and/or 19q13 on aCGH/WES. Our cohort exhibited IDH1-R132H mutations (5.4%), MGMT promotor methylation (34.6%), and mutations in ATRX (9.5%), TP53 (33.3%), and NOTCH1 (3.8%) but not in CIC (0%). In addition, MGMT methylation and ATRX mutation were significantly associated with clinical prognosis. In glioblastomas, partial deletions of 1p36 and/or 19q13 were uncommon, some of which appeared as 1p and/or 19q deletions on FISH analysis.
根据 2016 年世界卫生组织中枢神经系统肿瘤分类,在具有少突胶质细胞瘤样形态的神经胶质瘤的临床神经病理学中,检测 1p/19q 共缺失变得至关重要。在这里,我们使用荧光原位杂交(FISH)、阵列比较基因组杂交(aCGH)和/或全外显子组测序(WES)评估了 80 例包括 1p/19q 状态的胶质母细胞瘤的基因组谱。石蜡包埋的肿瘤组织进行 FISH 分析,同一肿瘤的相应冷冻组织用于评估 1p/19q 共缺失和其他遗传参数的 aCGH 和/或 WES,包括 IDH1-R132H、ATRX、TP53、CIC 和 NOTCH1 突变以及 MGMT 甲基化状态。我们还评估了 1p/19q 共缺失状态与分子标志物或临床结果之间的相关性。FISH 分析显示两例存在 1p/19q 共缺失,六例存在孤立的 1p 缺失,两例存在 19q 缺失,而 aCGH 和 WES 结果显示四例存在孤立的 19q 缺失,一例存在 19 单体。aCGH/WES 与 FISH 分析之间的 1p/19q 结果存在 11 例不一致,在大多数情况下,FISH 分析中的 1p 和/或 19q 缺失对应于 aCGH/WES 中 1p36 和/或 19q13 的部分缺失。我们的队列显示 IDH1-R132H 突变(5.4%)、MGMT 启动子甲基化(34.6%)以及 ATRX(9.5%)、TP53(33.3%)和 NOTCH1(3.8%)突变,但 CIC (0%)没有突变。此外,MGMT 甲基化和 ATRX 突变与临床预后显著相关。在胶质母细胞瘤中,1p36 和/或 19q13 的部分缺失并不常见,其中一些在 FISH 分析中表现为 1p 和/或 19q 缺失。