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Genomic landscape and distinct molecular subtypes of primary testicular lymphoma
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Genomic landscape and distinct molecular subtypes of primary testicular lymphoma
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Journal Article
Genomic landscape and distinct molecular subtypes of primary testicular lymphoma
2024
Overview
Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Aged
/ Analysis
/ Biomedical and Life Sciences
/ Cancer
/ DNA Copy Number Variations - genetics
/ Genes
/ Genomics
/ HLA
/ Humans
/ Lymphoma, Large B-Cell, Diffuse - classification
/ Lymphoma, Large B-Cell, Diffuse - genetics
/ Lymphoma, Large B-Cell, Diffuse - pathology
/ Male
/ Testicular Neoplasms - classification
/ Testicular Neoplasms - genetics
