Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients.
10.1007/s11684-023-0994-x
- Author:
Xianggui YUAN
1
;
Teng YU
1
;
Jianzhi ZHAO
1
;
Huawei JIANG
1
;
Yuanyuan HAO
1
;
Wen LEI
1
;
Yun LIANG
1
;
Baizhou LI
2
;
Wenbin QIAN
3
Author Information
1. Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
2. Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. alexlibz@126.com.
3. Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. qianwb@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
TMSB4X;
copy number variation;
gene mutation;
primary central nervous system lymphoma;
whole-genome sequencing
- MeSH:
Humans;
DNA Copy Number Variations;
Nuclear Proteins/genetics*;
Central Nervous System Neoplasms/pathology*;
Transcription Factors/genetics*;
Prognosis;
Lymphoma/genetics*;
Genomics;
China;
Central Nervous System/pathology*;
Bromodomain Containing Proteins;
Cell Cycle Proteins/genetics*
- From:
Frontiers of Medicine
2023;17(5):889-906
- CountryChina
- Language:English
-
Abstract:
Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.
