体细胞突变
BCL6公司
生物
免疫系统
癌症的体细胞进化
CDKN2A
祖细胞
生发中心
癌症研究
免疫学
B细胞
干细胞
遗传学
抗体
癌症
作者
G. Tjitske Los-de Vries,Phylicia Stathi,Ryanne Rutkens,Nathalie J. Hijmering,Jeroen A.C.W. Luijks,Patricia J.T.A. Groenen,Daphne de Jong,Bauke Ylstra,Margaretha G.M. Roemer
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2023-03-27
卷期号:83 (11): 1917-1927
被引量:5
标识
DOI:10.1158/0008-5472.can-22-3814
摘要
Large B-cell lymphoma of immune-privileged sites (LBCL-IP) arise in immune sanctuaries including the testis and central nervous system (CNS). After initially reaching complete response, relapses occur in almost 50% of patients, typically at other immune-privileged sites. Resolution of the clonal relationships and evolutionary patterns of LBCL-IP is required to understand the unique clinical behavior. We collected a unique set of 33 primary-relapse LBCL-IP sample pairs and performed next-generation sequencing for copy number, mutation, translocation, and immunoglobulin clonality analysis. All LBCL-IP sample pairs were clonally related, and both tumors developed from a common progenitor cell (CPC) with MYD88 and TBL1XR1 mutations and/or BCL6 translocations in 30/33 cases, indicating that these are early genetic events. This was succeeded by intermediate genetic events including shared, as well as unique alterations in targets of aberrant somatic hypermutation (aSHM), CD79B mutations, and 9p21.3/CDKN2A loss. Genetic alterations in genes involved in immune escape (HLA, CD274/PDCD1LG2) were predominantly unique in primary and relapse samples and thus considered late genetic events. Together, this study indicates that primary and relapsed LBCL-IP follow an early parallel evolutionary pattern where the CPC contains genetic alterations that support prolonged survival/proliferation and retention in a memory B-cell state, followed by germinal center reentry, aSHM and immune escape.Genomic analyses reveal that primary and relapse LBCL-IP originate from a common progenitor cell with a small set of genetic alterations, followed by extensive parallel diversification, elucidating the clonal evolution of LBCL-IP.
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