Mutational Pathogenicity Analysis toIdentify the Role and Pathogenicity of Gly۱۳۷Ser MissenseMutation in the Human CD۷۹B Gene Associated with DiffuseLarge B-cell Lymphoma (DLBCL)

Introduction: Diffuse large B cell lymphoma (DLBCL) isthe most common lymphoma. It typically presents as a rapidlygrowing mass or enlarging lymph nodes in a nodal or extra nodalsite. Due to the functional diversity of B-cells, it represents aheterogeneous group of diseases varying clinically and pathologically.DLBCL is one of these diseases that results in theclonal proliferation of a germinal or post-germinal malignantB cell. There are various variations in some genes involved inDLBCL. One of them is CD۷۹B. The protein of this gene is aB-cell antigen receptor complex-associated protein beta chainthat includes ۲۲۹ amino acids. The antigen receptor of B lymphocytes(BCR) plays important roles in virtually every stage inthe development, inactivation, or activation of B cells. Any nucleotidechanges in this gene are associated with several typesof lymphoma.Materials and Methods: In the CD۷۹B gene, the amino acidglycine is replaced with serine in position ۱۳۷ (p. Gly۱۳۷Ser;rs۱۲۱۹۱۲۴۲۴). This variation was predicted to be probablydamaging with a score of ۰.۹۸۲ by the PolyPhen-۲ programs. Itaffected the protein function with a score of ۰.۰۹۰ on the SIFT.The score obtained by Panther is ۰.۶۴۰, PHD-SNP is ۰.۷۵۲,SNAP is ۰.۷۵۰ and Meta SNP is ۰.۶۸۶. We evaluated predictionof protein stability changes upon single point mutation (DDG)with a score of -۰.۶۴ on I-Mutant۲. This variation was reportedas a pathogen by Clinvar. We analyzed the protein variation effectby PROVEAN with a score of -۵.۳. We predicted the impactfulmissense variants by MutPred with a score of ۰.۹۴۸.Results: Our results showed that the Gly۱۳۷Ser mutation inthe CD۷۹B gene is likely to have a detrimental effect on proteinfunction that may contribute to the development of Diffuse Large B-cell Lymphoma. The findings of this study providevaluable insights into the possible role of this mutation in thedevelopment and progression of lymphoma tumors, potentiallyleading to more effective diagnostic and treatment options foraffected individuals.

کلیدواژه ها:

Diffuse large B cell lymphoma ، DLBCL ، lymphoma ، CD۷۹B gene ، rs۱۲۱۹۱۲۴۲۴ ، B-cell antigen receptor