Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Neuro Oncol. 2022 May 4;24(5):834-846. doi: 10.1093/neuonc/noab246.
Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs.
Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH).
A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs.
12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.
中枢神经系统（CNS）生殖细胞瘤（GCT）主要发生在儿童和青年人群中。生殖细胞瘤通常对化疗和放疗有反应，而非生殖细胞瘤（NGGCT）则需要更强化的治疗。本研究旨在确定 12p 增益是否可以预测 CNS GCT 的预后。
本研究纳入了 82 例 CNS GCT 患者。12p 增益的定义是在潜在的多倍体或多倍性背景下额外出现 12p。通过 Illumina 甲基化 450K 芯片进行拷贝数研究，并通过荧光原位杂交（FISH）进行验证，对病例进行分析。
在 82 例病例中，发现 25 例（30%）存在 12p 增益，且在 NGGCT 中更为常见（生殖细胞瘤病例中有 12%，而 NGGCT 病例中有 50%），特别是存在恶性成分的病例，如未成熟畸胎瘤、卵黄囊瘤、绒毛膜癌和胚胎癌。12p 增益和 KIT 突变是相互排斥的事件。12p 增益的存在与较短的无进展生存期（PFS）和总生存期（OS）相关（10 年 OS：有和无 12p 增益的分别为 59%和 94%，P = 0.0002），即使将组织学和肿瘤标志物纳入多变量分析也是如此。在 NGGCT 中，12p 增益对 PFS 和 OS 仍然具有预后意义（10 年 OS：分别为 47%和 90%，P = 0.02）。混合 GCT 中，12p 拷贝数状态在组织学成分之间是共享的。
12p 增益可能预示着 NGGCT 中恶性成分的存在和患者预后不良。它可能与 CNS GCT 的早期肿瘤发生有关。
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