Whole genome sequencing identified new somatic mutations for chronic myelomonocytic leukemia.

OBJECTIVE We aimed to gain new insight into the molecular alterations of Chronic Myelomonocytic Leukemia (CMML). PATIENTS AND METHODS We performed whole-genome sequencing (WGS) and subsequent Sanger sequencing validation analysis in three individuals with CMML. Genomic DNA samples from bone marrow and matching buccal mucosa samples were sequenced. RESULTS For all six samples, a total of 806.43 Gb data were generated, achieving a minimum mean depth of 30.76. A total of 22 somatic variants were found to be protein-altering, including 1 exonic frame shift indel, 18 missense SNVs, 2 stop gain SNVs, and 1 stop loss SNV. We focused on the five novel variants which have not been reported in known databases and successfully validated three missense SNVs in AKAP4, COL2A1, and MAML1, respectively. CONCLUSIONS WGS analyzes provided us a new insight into the molecular events governing the pathogenesis of CMML. The somatic variants we reported here may provide new targets for further therapeutic studies.