| Literature DB >> 35528192 |
Marco Magistri1, Lanie E Happ2, Jeremy Ramdial1, XiaoQing Lu1, Vasileios Stathias3,4, Kranthi Kunkalla5, Nitin Agarwal5, Xiaoyu Jiang1, Stephan C Schürer3,4, Sander R Dubovy6, Jennifer R Chapman5, Francisco Vega5, Sandeep Dave2, Izidore S Lossos1,3.
Abstract
A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets.Entities:
Keywords: CABIN1; MEF2B; Marginal zone lymphoma; NFAT; Orbital adnexa lymphoma
Year: 2021 PMID： 35528192 PMCID： PMC9075502 DOI： 10.1158/2767-9764.crc-21-0022
Source DB: PubMed Journal: Cancer Res Commun ISSN： 2767-9764