Neurological Surgery 脳神経外科51巻5号

2023年09月発行

特集 臨床脳神経外科医にとってのWHO脳腫瘍分類第5版 Ⅳ 小児脳腫瘍

胚細胞腫の分子生物学的特徴と臨床的意義

著者： 髙見浩数¹

所属機関： ¹東京大学医学部附属病院脳神経外科

ページ範囲：P.892 - P.900

Point
・半数以上の症例でRTK，MAPK，PI3K経路の遺伝子変異を有するが，構造異常は現在解明が進んでいる．
・ジャーミノーマはゲノム全体にわたる低メチル化が特徴で，起源細胞とされる始原生殖細胞と類似する．
・ジャーミノーマにおける腫瘍細胞含有率とノンジャーミノーマにおける12p gainは予後と相関し，今後の治療層別化因子になり得る．

参考文献

1）Jennings MT, et al：Intracranial germ-cell tumors：natural history and pathogenesis. J Neurosurg 63：155-167, 1985

2）Matsutani M, et al：Primary intracranial germ cell tumors：a clinical analysis of 153 histologically verified cases. J Neurosurg 86：446-455, 1997

3）Takami H, et al：Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium. Neuro Oncol 21：1565-1577, 2019

4）Brain Tumor Registry of Japan（2005-2008）. Neurol Med Chir（Tokyo）57（Suppl 1）：9-102, 2017

5）Takami H, et al：The third eye sees double：cohort study of clinical presentation, histology, surgical approaches, and ophthalmic outcomes in pineal region germ cell tumors. World Neurosurg 150：e482-e490, 2021　doi:10.1016/j.wneu.2021.03.030

6）Takami H, et al：Epidemiology, natural history, and optimal management of neurohypophyseal germ cell tumors. J Neurosurg 134：437-445, 2021

7）Sonoda Y, et al：Germ cell tumors in the basal ganglia：problems of early diagnosis and treatment. J Neurosurg Pediatr 2：118-124, 2008

8）Louis DN, et al：The 2021 WHO classification of tumors of the central nervous system：a summary. Neuro Oncol 23：1231-1251, 2021

9）Ogino H, et al：CNS germinoma with elevated serum human chorionic gonadotropin level：clinical characteristics and treatment outcome. Int J Radiat Oncol Biol Phys 62：803-808, 2005

10）Fukuoka K, et al：Human chorionic gonadotropin detection in cerebrospinal fluid of patients with a germinoma and its prognostic significance：assessment by using a highly sensitive enzyme immunoassay. J Neurosurg Pediatr 18：573-577, 2016

11）Matsutani M：Clinical management of primary central nervous system germ cell tumors. Semin Oncol 31：676-683, 2004

12）Bartels U, et al：Phase Ⅱ trial of response-based radiation therapy for patients with localized germinoma：a Children's Oncology Group study. Neuro Oncol 24：974-983, 2022

13）Calaminus G, et al：SIOP CNS GCT 96：final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro Oncol 15：788-796, 2013

14）Fangusaro J, et al：Phase Ⅱ trial of response-based radiation therapy for patients with localized CNS nongerminomatous germ cell tumors：a Children's Oncology Group study. J Clin Oncol 37：3283-3290, 2019

15）Calaminus G, et al：Outcome of patients with intracranial non-germinomatous germ cell tumors-lessons from the SIOP-CNS-GCT-96 trial. Neuro Oncol 19：1661-1672, 2017

16）Wang L, et al：Novel somatic and germline mutations in intracranial germ cell tumours. Nature 511：241-245, 2014

17）Ichimura K, et al；Intracranial Germ Cell Tumor Genome Analysis Consortium：Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy. Acta Neuropathol 131：889-901, 2016

mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol 127：911-925, 2014

19）Satomi K, et al：12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors. Neuro Oncol 24：834-846, 2022

20）Takami H, et al：Transcriptome and methylome analysis of CNS germ cell tumor finds its cell-of-origin in embryogenesis and reveals shared similarities with testicular counterparts. Neuro Oncol 24：1246-1258, 2022

21）Fukushima S, et al；Intracranial Germ Cell Tumor Genome Analysis Consortium（The iGCTConsortium）：Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol 133：445-462, 2017

22）Nakano T, et al：GCT-62. Dissecting intratumoral heterogeneity of central nervous system germ cell tumors by single-cell RNA-sequencing. Neuro Oncol 22（Suppl 3）：iii340-iii341, 2020　doi:10.1093/neuonc/noaa222.279

23）Takami H, et al：Low tumor cell content predicts favorable prognosis in germinoma patients. Neurooncol Adv 3：vdab110, 2021　doi:10.1093/noajnl/vdab110

24）Takami H, et al；Intracranial Germ Cell Tumor Genome Analysis Consortium（the iGCT Consortium）：Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance. Neuropathol Appl Neurobiol 46：111-124, 2020