Methods and compositions for use of driver mutations in cll
Broad Case No.
List of inventors -
Applicants identified (44) recurrently mutated genes and (11) recurrent somatic copy number variations (CNV) through whole-exome sequencing of 538 chronic lymphocytic leukemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized cancer drivers (RPS15, IKZF3) and collectively identify RNA processing and export, MYC activity and MAPK signaling as central pathways involved in CLL. Clonality analysis of this large dataset further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pretreatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. The discovery of novel cancer genes and the network of relationships between the driver events and their impact on disease relapse and clinical outcome provide novel treatment options.