ANALYSIS OF THE 3΄UTR REGION OF THE NOTCH1 GENE IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS

Abstract

Detection of mutations in the 3'UTR region of the NOTCH1was performed by direct sequencing in 87previously untreated CLL patients (from the total group of 237CLL patients) with unmutated immunoglobulin heavy-chain variable (UM IGHV) genes and without mutations in hotspot regions of TP53, SF3B1, and exon 34of NOTCH1genes. Mutations in the 3'UTR region of the NOTCH1were revealed in three of 87CLL patients (3.4%). Two cases with non-coding mutations were related to subset #1of stereotyped B-cell receptors, and one case belonged to stereotyped subset #28a. Analysis with inclusion of 30UM IGHV cases with previously detected c.7544_7545delCT mutations revealed that the frequency of UM IGHV genes of I phylogenetic clan (except IGHV1-69) was significantly increased, and the frequency of UM IGHV3and IGHV4genes, on the contrary, was reduced in NOTCH1-mutated cases comparing with NOTCH1-unmutated cases (p = 0.002) and the general group (p = 0.013). SNP rs3124591did not affect the risk of CLL and survival parameters of the patients. At the same time, differences were found in the frequency of IGHV gene usage and in the structure of HCDR3in carriers of individual genotypes. The frequency of NOTCH1mutations in 3'UTR region was low. Our findings confirmed current data on the association between the structure of the B-cell receptor and the appearance of NOTCH1mutations. Some features of HCDR3structure were identified in carriers of TT and CC genotypes of rs3124591.