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Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression.
Chen, Zegeng; Huang, He; Hong, Huangming; Huang, Huageng; Weng, Huawei; Yu, Le; Xiao, Jian; Wang, Zhao; Fang, Xiaojie; Yao, Yuyi; Yue, Jia-Xing; Lin, Tongyu.
Afiliação
  • Chen Z; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Huang H; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Hong H; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Huang H; Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
  • Weng H; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Yu L; Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
  • Xiao J; Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
  • Wang Z; Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, China.
  • Fang X; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Yao Y; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Yue JX; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • Lin T; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. yuejiaxing@gmail.com.
Genome Med ; 16(1): 48, 2024 04 02.
Article em En | MEDLINE | ID: mdl-38566223
ABSTRACT

BACKGROUND:

Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored.

METHODS:

Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels.

RESULTS:

Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole.

CONCLUSIONS:

The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfoma Extranodal de Células T-NK Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfoma Extranodal de Células T-NK Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article