A Quantitative Analysis of Subclonal and Clonal Gene Mutations before and after Therapy in Chronic Lymphocytic Leukemia.

ABSTRACT:

Purpose

Chronic lymphocytic leukemia (CLL)-associated gene mutations that influence CLL cell fitness and chemotherapy resistance should increase in clonal representation when measured before therapy and at relapse.

Experimental design

To uncover mutations associated with CLL relapse, we have performed whole-exome sequencing in a discovery cohort of 61 relapsed CLL patients identifying 86 recurrently mutated genes. The variant allele fractions (VAF) of 19 genes with mutations in ≥3 of 61 cases were measured in 53 paired pre- and posttreatment CLL samples sorted to purity using panel-based deep resequencing or by droplet digital PCR.

Results

We identify mutations in TP53 as the dominant subclonal gene driver of relapsed CLL often demonstrating substantial increases in V

SUBMITTER: Amin NA 

PROVIDER: S-EPMC5010528 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature