Whole-exome sequencing of rectal neuroendocrine tumors

被引:5
作者
Li, Yuanliang [1 ]
Guo, Yiying [2 ]
Cheng, Zixuan [1 ]
Tian, Chao [1 ]
Chen, Yingying [1 ]
Chen, Ruao [1 ]
Yu, Fuhuan [1 ]
Shi, Yanfen [3 ]
Su, Fei [4 ]
Zhao, Shuhua [5 ]
Wang, Zhizheng [6 ]
Luo, Jie [3 ]
Tan, Huangying [1 ,2 ,4 ]
机构
[1] Beijing Univ Chinese Med, China Japan Friendship Hosp, Dept Integrat Oncol, Beijing, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, China Japan Friendship Hosp, Dept Integrat Oncol, Beijing, Peoples R China
[3] China Japan Friendship Hosp, Dept Pathol, Beijing, Peoples R China
[4] China Japan Friendship Hosp, Dept Integrat Oncol, Beijing, Peoples R China
[5] HaploX Biotechnol Co Ltd, Dept Biol Informat Res, Shenzhen, Guangdong, Peoples R China
[6] HaploX Biotechnol Co Ltd, Acad Dept, Shenzhen, Guangdong, Peoples R China
关键词
rectal neuroendocrine tumors; whole-exome sequencing; prognosis; targeted therapy; immune checkpoint blockade; CANCER; LANDSCAPE; LUNG; RESISTANCE; MUTATIONS;
D O I
10.1530/ERC-22-0257
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The genetic characteristics of rectal neuroendocrine tumors (R-NETs) were poorly understood. Depicting the genetic characteristics may provide a biological basis for prognosis prediction and novel treatment development. Tissues of 18 R-NET patients were analyzed using whole-exome sequencing. The median tumor mutation burden (TMB) and microsatellite instability (MSI) were 1.15 Muts/MB (range, 0.03-23.28) and 0.36 (range, 0.00-10.97), respectively. Genes involved in P53 signaling, PI3K-AKT signaling, DNA damage repair, WNT signaling, etc. were frequently altered. Higher TMB (P = 0.078), higher CNV (P = 0.110), somatic mutation of CCDC168 (P = 0.049), HMCN1 (P = 0.040), MYO10 (P = 0.007), and amplification of ZC3H13 (P < 0.001) were associated with shorter OS. Potentially targetable gene alterations (PTGAs) were seen in 72% of the patients. FGFR1 amplification (22%) was the most common PTGA followed by BARD1 and BRCA2 mutation (each 17%). As for gene variations associated with the efficacy of immune checkpoint blockade (ICB), FAT1 alteration (39%) and PTEN depletion (28%) were commonly observed. In conclusion, frequently altered oncogenic pathways might contribute to the development and progression of R-NETs. Gene alterations significantly associated with prognosis might be potential novel targets. Targeted therapy might be a promising strategy as targetable alterations were prevalent in R-NETs. FAT1 alteration and PTEN depletion might be the main genetic alterations influencing the response to ICB besides overall low TMB and MSI in R-NETs.
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页数:15
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