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.
基金：
National Cancer Institute of the National Institutes of
Health under grant number P30CA033572. It was also partly supported by Start-up
funds from the City of Hope National Medical Center, the Dr. Norman and Melinda
Payson Professorship in Hematologic Cancers and the Toni Stephenson Lymphoma
Center; Beijing Natural Science Funding (No. 7132062) and Beijing Golden Bridge
Engineer Seed Funding (No. 2014-37) awarded to GD.
第一作者机构：[1]City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA[2]Capital Med Univ, Beijing Tongren Hosp, Dept Pathol, Beijing 100730, Peoples R China[3]Capital Med Univ, Beijing Tiantan Hosp, Dept Pathol, Beijing 100070, Peoples R China
医学