Driver mutations in ADGRL3 are involved in the evolution of ependymoma.
Jing WangShao-Yan XiQi ZhaoYun-Fei XiaQun-Ying YangHai-Ping CaiFang WangYi-Ying ZhaoHuan-Jing HuZhi-Hui YuFu-Rong ChenPeng-Fei XuRi-Zhen XuJian WangJi ZhangChao KeXiang-Heng ZhangFu-Hua LinCheng-Cheng GuoYan-Chun LvCong LiHai-Tao XieQian CuiHong-Mei WuYan-Hui LiuZhi LiHong-Kai SuJing ZengFu HanZhao-Jie LiKe SaiZhong-Ping ChenPublished in: Laboratory investigation; a journal of technical methods and pathology (2022)
Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.
Keyphrases
- genome wide
- end stage renal disease
- single cell
- ejection fraction
- binding protein
- newly diagnosed
- dna methylation
- chronic kidney disease
- poor prognosis
- copy number
- free survival
- peritoneal dialysis
- multiple sclerosis
- long non coding rna
- coronary artery disease
- escherichia coli
- staphylococcus aureus
- patient reported outcomes
- percutaneous coronary intervention
- biofilm formation
- cerebral ischemia
- fine needle aspiration
- ultrasound guided