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两例复发性胶质瘤发生从少突胶质细胞瘤到星形细胞瘤的谱系转换

Recurrent Glioma With Lineage Conversion From Oligodendroglioma to Astrocytoma in Two Cases.

作者信息

Kim Jo-Heon, Jang Woo-Youl, Jung Tae-Young, Jung Shin, Kim Kyung-Keun, Kim Hyung-Seok, Kim Eun-Hee, Lee Min-Cheol, Moon Kyung-Sub, Lee Kyung-Hwa

机构信息

Department of Pathology, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Hwasun, South Korea.

Department of Neurosurgery, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Hwasun, South Korea.

出版信息

Front Oncol. 2019 Aug 27;9:828. doi: 10.3389/fonc.2019.00828. eCollection 2019.

Abstract

Following the introduction of the molecular classification of gliomas by the WHO in 2016, molecularly-proven lineage conversion during glioma recurrence has never been reported. The reported two cases were initially diagnosed as oligodendroglioma with 1p/19q-codeletion and mutation of -R132H. The recurrent tumors showed loss of alpha-thalassemia/mental retardation X-linked (ATRX) expression, strong P53 positivity, and 1p/19q-nondeletion. Next generation sequencing analysis performed on the first case confirmed the transition of molecular traits from oligodendroglioma to astrocytoma. An mutation of R132H was preserved in the episodes of recurrence, but and mutations were newly acquired and promoter mutation C228T was lost at the most recent recurrence. The issue in question for the presented cases is whether the original tumors were pure oligodendrogliomas that then transdifferentiated into astrocytomas, or whether the original tumor was an oligoastrocytoma having oligodendroglioma cells that outnumbered the astrocytoma cells and where the astrocytoma cells becoming more dominant over the episodes of recurrence. With the recognition of the possibility of lineage conversion, our study suggests that molecular examination should be performed to adjust therapeutic strategies in recurrent gliomas. Indeed, our observation of lineage conversion in glioma recurrence calls into question the current distinction drawn between oligodendroglioma, astrocytoma and oligoastrocytoma, rather than simply bidding "farewell to oligoastrocytoma."

摘要

2016年世界卫生组织(WHO)引入胶质瘤分子分类后,尚未有胶质瘤复发过程中经分子证实的谱系转化的报道。所报道的两例病例最初被诊断为伴有1p/19q共缺失和-R132H突变的少突胶质细胞瘤。复发肿瘤显示α地中海贫血/智力发育迟缓X连锁(ATRX)表达缺失、P53强阳性以及1p/19q非共缺失。对第一例病例进行的二代测序分析证实了分子特征从少突胶质细胞瘤向星形细胞瘤的转变。R132H突变在复发过程中得以保留,但在最近一次复发时新获得了 和 突变,且 启动子突变C228T丢失。所呈现病例的问题在于,最初的肿瘤是纯粹的少突胶质细胞瘤而后转分化为星形细胞瘤,还是最初的肿瘤是少突星形细胞瘤,其中少突胶质细胞瘤细胞数量超过星形细胞瘤细胞,且在复发过程中星形细胞瘤细胞变得更占优势。随着认识到谱系转化的可能性,我们的研究表明,对于复发性胶质瘤应进行分子检查以调整治疗策略。的确,我们对胶质瘤复发中谱系转化的观察对目前少突胶质细胞瘤、星形细胞瘤和少突星形细胞瘤之间的区分提出了质疑,而不仅仅是简单地“告别少突星形细胞瘤”。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e17e/6719522/5c171b4919a9/fonc-09-00828-g0001.jpg

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