Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma Arising From the Kidney

Abstract

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney were extremely rare, genetic alteration or molecular features was not yet explored, which may lead to limited choices for postoperative adjuvant or targeted. Whole-exome sequencing based tumor mutation profiling was performed on the tumor sample from a 77-year-old female presenting with discomfort at the waist was pathologically diagnosed as MALT lymphomas in the right kidney. We identified 101 somatic SNVs, and the majority of the identified SNVs were located in CDS and intronic regions. A total of 190 gain counts of CNVs with a total size of 488,744,073 was also investigated. After filtering with the CGC database, seven predisposing genes (ARID4A, COL2A1, FANCL, ABL2, HSP90AB1, FANCA, and DIS3) were found in renal MALT specimen. Furthermore, we compared somatic variation with known driver genes and validated three mutational driver genes including ACSL3, PHOX2B, and ADCY1. Sanger sequencing of germline DNA revealed the presence of a mutant base T of PHOX2B and a mutant base C of ADCY1 in the sequence, which were discovered for the first time in MALT lymphomas involving the kidney. Moreover, immunohistochemical analysis revealed that tumor cells were positive for CD20, CD79a, PAX5, CD21, and CD23, and expression of CD3, CD5, and CD8 were observed in reactive T lymphocytes surrounding tumor cells. These findings illustrated that concurrent aberrant PHOX2B and ADCY1 signaling may be a catastrophic event resulting in disease progression and inhibition of the putative driver mutations may be alternative adjuvant therapy for MALT lymphoma in the kidney which warrants further clinical investigation.

Analysis of Genetic Alterations in Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma With Whole-Exome Sequencing

“…Two alterations of TMEM127 were both frameshift deletions ( Figures 1D , 2 ), which may be accompanied by loss of the wildtype allele in tumor DNA, consistent with a classic tumor suppressor gene mode of inactivation ( 27 ). DIS3 was found recurrently mutated in this cohort, consistent with a recent study that described DIS3 as a predisposing gene mutated in renal MALT ( 28 , 29 ). Although described as a tumor suppressor in various cancers, FAT1 was few found mutated in lymphoma entities to date ( 30 – 32 ).…”

Recent Advances in the Genetic of MALT Lymphomas

“…Other studies analyzing the mutational landscape of MALT lymphomas at several sites have been conducted and the list of involved genes keeps growing [ 193 ].…”

Molecular profiling of primary renal diffuse large B-cell lymphoma unravels a proclivity for immune-privileged organ-tropism

“…Insufficient characterization of pathogenetic mechanisms in indolent PR-DLBCL derives from limited data, primarily comprised of small case series and a lack of in-depth molecular characterization of patients and samples 11 . Molecular drivers of lymphomas originating from organs lacking an intrinsic lymphatic niche, such as the kidney, remain widely elusive apart from individual case studies 12 . To elucidate the genetic and transcriptional landscape and drivers of PR-DLBCL, we conducted a comprehensive investigation employing whole exome sequencing (WES), array-based analysis of somatic copy number alterations (SCNA), and RNA sequencing (RNA-seq) to unravel both molecular properties of this rare entity as well as the cellular composition of its tumor microenvironment (TME).…”