基因组不稳定性
神经母细胞瘤RAS病毒癌基因同源物
免疫系统
转录组
克拉斯
生物
体细胞
MAPK/ERK通路
癌症研究
突变
DNA损伤
遗传学
基因
DNA
信号转导
基因表达
作者
Bo Li,Shuang Zhao,Shouwei Li,Chunde Li,Wei Liu,Lin Liu,Bowen Cui,Xing Liu,Huiyuan Chen,Jing Zhang,Rong Yin,Fei Liu,Ming Yang,Tao Jiang,Yu Liu,Xiaoguang Qiu
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2024-03-02
标识
DOI:10.1093/neuonc/noae038
摘要
Intracranial germ cell tumours (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumours (NGGCTs). Previous studies have found that somatic mutations involving the MAPK/mTOR signalling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking.We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing.We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: immune-hot, MYC/E2F and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signalling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumours showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs.Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.
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