Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany; Department of Neurosurgery, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.
Eur J Cancer. 2019 Jun;114:27-35. doi: 10.1016/j.ejca.2019.03.019. Epub 2019 Apr 22.
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive paediatric brain tumour with fatal outcome. The Individualised Therapy For Relapsed Malignancies In Childhood (INFORM) registry study offers comprehensive molecular profiling of high-risk tumours to identify target alterations for potential precision therapy. We analysed molecular characteristics and clinical data after brainstem biopsy of all enrolled newly diagnosed DIPGs.
From -February 2015 to February 2018, 21 subsequent primary DIPG cases were enrolled in the nation-wide multicentre INFORM registry study after brainstem biopsy. Whole-genome, whole-exome sequencing and DNA methylation analysis were performed, and RNA-sequencing was added in case of sufficient material. Clinical data were obtained from standardised questionnaires and the INFORM clinical data bank.
Tumour material obtained from brainstem biopsy was sufficient for DNA analysis in all cases and RNA analysis in 16 of 21 cases. In 16 of 21 cases (76%), potential targetable alterations were identified including highly relevant MET and NTRK1 fusions as well as an EZH2 alteration not previously described in DIPG. In 5 of 21 cases, molecular information was used for initiation of targeted treatment. The majority of patients (19/21) presented with neurological deficits at diagnosis. Newly arising or worsening of neurological deficits post-biopsy occurred in nine patients. Symptoms were reversible or improved notably in eight cases.
In this multicentre study setting, brainstem biopsy of DIPG was feasible and yielded sufficient material for comprehensive molecular profiling. Relevant molecular targets were identified impacting clinical management in a substantial subset. Death or severe bleeding occurred in none of the cases. One of 20 patients experienced unilateral paraesthesia possibly related to biopsy.
弥漫性内在脑桥神经胶质瘤（DIPG）是一种具有致命结局的高度侵袭性小儿脑肿瘤。个体化儿童复发性恶性肿瘤治疗（INFORM）登记研究提供了高危肿瘤的全面分子分析，以确定潜在精准治疗的目标改变。我们分析了所有入组的新诊断 DIPG 患者经脑干活检后的分子特征和临床数据。
从 2015 年 2 月至 2018 年 2 月，21 例后续原发性 DIPG 病例在全国多中心 INFORM 登记研究中经脑干活检入组。进行了全基因组、全外显子组测序和 DNA 甲基化分析，并在有足够材料的情况下增加了 RNA 测序。临床数据来自标准化问卷和 INFORM 临床数据库。
所有病例均获得足够的脑干活检组织进行 DNA 分析，21 例中有 16 例进行 RNA 分析。在 21 例中的 16 例（76％）中，确定了潜在的可靶向改变，包括高度相关的 MET 和 NTRK1 融合，以及以前在 DIPG 中未描述的 EZH2 改变。在 21 例中有 5 例，分子信息用于开始靶向治疗。大多数患者（21 例中有 19 例）在诊断时存在神经功能缺损。9 例患者在活检后出现新的或恶化的神经功能缺损。8 例症状可逆或明显改善。
在这个多中心研究中，DIPG 的脑干活检是可行的，为全面的分子分析提供了足够的材料。在相当一部分患者中，确定了相关的分子靶点，影响了临床管理。在没有一个病例中发生死亡或严重出血。20 例患者中有 1 例出现单侧感觉异常，可能与活检有关。
