成人髓母细胞瘤：细胞遗传学表型可识别预后亚组。
Medulloblastoma in Adults: Cytogenetic Phenotypes Identify Prognostic Subgroups.
机构信息
From the Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
Division of Pediatric Oncology and Hematology, University Children's Hospital Rostock, Rostock, Germany.
出版信息
J Neuropathol Exp Neurol. 2021 Apr 16;80(5):419-430. doi: 10.1093/jnen/nlab020.
Adult medulloblastomas (MB) are rare. We investigated the genetic landscape and prognostic impact of genetic aberrations in a cohort of 117 adult medulloblastomas. Histological features and pathway activation were evaluated at the protein level; 14.5% showed wingless-type activation, 63.3% SHH activation, and 22.2% were classified as non-WNT/non-SHH-MB. Genome-wide copy number analysis was performed by molecular inversion probe array technology. MB-related genes were sequenced in WNT- and SHH-activated MBs. 79.7% of SHH-MBs showed desmoplastic/nodular histology; all other MBs had classic histology. WNT-MBs carried oncogenic CTNNB1 mutations in 88.2% and had monosomy 6 in 52.9%. In SHH-MBs, TERT promoter mutations occurred in 97%, mutations in PTCH1 in 38.2%, SMO in 15.5%, SUFU in 7.4%, and TP53-mutations in 4.1%. In all, 84.6% of non-WNT/non-SHH-MBs had an isochromosome 17q. A whole chromosomal aberration (WCA) signature was present in 45.1% of SHH-TP53-wild type (wt)-MBs and 65.4% of non-WNT/non-SHH-MBs. In 98 cases with survival data, WNT-MBs had a 5-year overall survival (OS) of 68.6%. SHH-MBs TP53wt type and non-WNT/non-SHH-MBs showed 5-year OS of 80.4% and 70.8%, respectively. TP53-mutant SHH-MBs represented a prognostically unfavorable entity; all patients died within 5 years. Patients with a WCA signature showed significantly increased OS (p = 0.011 for SHH-TP53wt-MBs and p = 0.048 for non-WNT/non-SHH-MBs).
成人髓母细胞瘤（MB）较为罕见。我们在 117 例成人髓母细胞瘤患者队列中研究了遗传异常的遗传图谱和预后影响。通过蛋白质水平评估组织学特征和通路激活；14.5%表现为无翅型激活，63.3%表现为 SHH 激活，22.2%被归类为非 WNT/非 SHH-MB。通过分子反转探针阵列技术进行全基因组拷贝数分析。对 WNT 和 SHH 激活的 MB 进行 MB 相关基因测序。79.7%的 SHH-MB 表现为间变性/结节性组织学；所有其他 MB 均为经典组织学。WNT-MB 携带致癌 CTNNB1 突变，占 88.2%，单体 6 缺失占 52.9%。在 SHH-MB 中，TERT 启动子突变发生率为 97%，PTCH1 突变发生率为 38.2%，SMO 突变发生率为 15.5%，SUFU 突变发生率为 7.4%，TP53 突变发生率为 4.1%。所有非 WNT/非 SHH-MB 中有 84.6%存在 17q 等臂染色体。在 45.1%的 SHH-TP53wt-MB 和 65.4%的非 WNT/非 SHH-MB 中存在全染色体畸变（WCA）特征。在有生存数据的 98 例患者中，WNT-MB 的 5 年总生存率（OS）为 68.6%。SHH-MB 的 TP53wt 型和非 WNT/非 SHH-MB 的 5 年 OS 分别为 80.4%和 70.8%。TP53 突变型 SHH-MB 是预后不良的实体；所有患者均在 5 年内死亡。具有 WCA 特征的患者 OS 显著提高（SHH-TP53wt-MB 为 p=0.011，非 WNT/非 SHH-MB 为 p=0.048）。
Zotero 插件