CLL-299 Novel Missense Single Nucleotide Polymorphisms of Human CD38 Gene Allied to Chronic Lymphocytic Leukemia: A Bioinformatics Approach.

CONTEXT: B-cell chronic lymphocytic leukemia (CLL) is a hematological malignancy that develops from abnormal lymphoid stem cells in the bone marrow and secondary lymphoid tissue (B-lymphocytes). One of the significant contributors to the pathogenesis of CLL is a mutation of CD38 protein. CD38 is a multifunctional ectoenzyme expressed in B-lymphocytes, with a poorly understood in the pathogenesis of CLL.

OBJECTIVE AND DESIGN: Here we aimed to bioinformatically appraise CD38 missense single nucleotide polymorphisms allied to CLL and to predict their effect on the structure and function of CD38 protein.

METHOD AND RESULTS: A literature review identified two SNPs in the CD38 gene that had been discovered by PCR of patients with CLL. Functional analysis by SIFT, Polyphen2, and PROVEAN revealed nine deleterious SNPs in the CD38 coding region. These SNPs were further analyzed by SNAP2, SNP@GO. PMut, STRING, and other software packages which confirmed nine of those SNPs to be truly pathogenic. Stability analysis performed using I-Mutant identified seven SNPs that were predicted to decrease the stability of CD38 and two SNPs predicted to increase it; while MUpro identified eight SNPs that were predicted to decrease the stability of the protein and one SNP that was predicted to increase it. Physiochemical analysis was done using Project HOPE to visualize the most significant SNPs using the Chimera software. Finally, the following SNPs (S193C, D147G, and P98L) were predicted as deleterious in relation to the structure and function of CD38 protein by most of the software used in this study.

CONCLUSIONS: We reported three novel driver SNPs in the CD38 gene that could result in deleterious effects on protein structure. This genetic variation might eventually alter the molecular functions of CD38 protein implicated in the development of CLL.