Mutations Identified Using NGS Comprise the Overwhelming Majority of Disruptions in CLL: Results From a Multicentre Study.

Limited data exists to show the correlation of (tumour protein 53) mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by FISH and mutations by NGS before treatment. Using a 10% variant allele frequency (VAF) threshold, cases were segregated into high burden mutations (≥10%) and low burden mutations (<10%). aberrations (17p [del(17p)] and/or mutation) were detected in 320/2332 patients (13.7%). Using NGS analysis, 429 mutations were identified in 303 patients (13%). Of these 238 (79%) and 65 (21%) were cases with high burden and low burden mutations respectively. In our cohort, 2012 cases did not demonstrate a aberration (86.3%). A total of 159 cases showed mutations in the absence of del(17p) (49/159 with low burden mutations) and 144 cases had both mutation and del(17p) (16/144 with low burden mutations). Only 17/2332 (0.7%) cases demonstrated del(17p) with no mutation. Validated NGS protocols should be used in clinical decision making to avoid missing low-burden mutations and can detect the vast majority of aberrations.