Genomic Profiling Identifies Distinct Genetic Subtypes in Extra-nodal Natural Killer/T-cell Lymphoma

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2022 Jun 13

PMID 35697790

Authors

Gehong Dong

Xuxiang Liu

Lifu Wang

Wenjuan Yin

Alyssa Bouska

Qiang Gong

Kunal Shetty

Lu Chen

Sunandini Sharma

Jibin Zhang

Carmen Lome-Maldonado

Leticia Quintanilla-Martinez

Yuping Li

Joo Y Song

Wenyan Zhang

Yunfei Shi

Jinhui Wang

Lingbo Kong

Xiwei Wu

Jingwen Wang

Hong-Gang Liu

Lingfei Kong

Wenyong Sun

Weiping Liu

Lili Wang

Timothy W McKeithan

Javeed Iqbal

Wing C Chan

Affiliations

Soon will be listed here.

Abstract

Extra-nodal NK/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive Epstein-Barr virus associated lymphoma, typically presenting in the nasal and paranasal areas. We assembled a large series of ENKTCL (n = 209) for comprehensive genomic analysis and correlative clinical study. The International Lymphoma Prognostic Index (IPI), site of disease, stage, lymphadenopathy, and hepatomegaly were associated with overall survival. Genetic analysis revealed frequent oncogenic activation of the JAK/STAT3 pathway and alterations in tumor suppressor genes (TSGs) and genes associated with epigenomic regulation. Integrated genomic analysis including recurrent mutations and genomic copy number alterations using consensus clustering identified seven distinct genetic clusters that were associated with different clinical outcomes, thus constituting previously unrecognized risk groups. The genetic profiles of ENTKCLs from Asian and Hispanic ethnic groups showed striking similarity, indicating shared pathogenetic mechanism and tumor evolution. Interestingly, we discovered a novel functional cooperation between activating STAT3 mutations and loss of the TSG, PRDM1, in promoting NK-cell growth and survival. This study provides a genetic roadmap for further analysis and facilitates investigation of actionable therapeutic opportunities in this aggressive lymphoma.

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