PB1659 WHOLE EXOME SEQUENCING IN ADULT PATIENT WITH PHILADELPHIA / BCR‐ABL1 POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

Abstract

Background:BCR‐ABL1 gene fusion is detected at approximately 20% of adult acute lymphoblastic leukemia (ALL). Patients with Philadephia (Ph) / BCR‐ABL1 positive are a high risk group that associated with poor prognosis and short duration remission. Patients showed markedly improved with introduction of tyrosine kinase inhibitor combined with chemotherapy regimen but a small fraction of these patients remain refractory and poor response to treatment.Aims:The aim of this study was to determine the somatic mutations profile using whole exome sequencing of patient with Ph‐positive ALL.Methods:DNA from matched tumour‐normal samples for four patients with Ph‐positive ALL was extracted from peripheral blood or bone marrow leukemia cells by QIAamp DNA Mini kit. The exome library was enriched using the Nextera Rapid Capture Expended Enrichement kit (Illumina, San Diego, CA) according to the manufacturer's protocol and were subsequently sequenced on Illumina HiSeq 2500 system. Somatic mutations were separated from germline variants using Genome Analaysis Toolkits (GATK) best practices filtering strategy.Results:We identified a total of 14,804 intragenic somatic mutations (range from 2,948 to 4,165 in each). Of these 760 variants were passed through the variant caller. Among them 462 were single nucleotide variants (SNVs) and 298 were insertion/deletions (InDels). Total of 48 common variants were observed but failed Mutect caller. Among SNVs, 110 variants were nonsynonymous, 46 synonymous, 6 stopgain, 3 unknown and majority 297 (64.3%) null variants. A total of 53 nonsynonymous SNVs and 14 InDeLs (8 were frameshift deletion, 5 frameshift insertion and one stopgain) were identified as possible pathogeneic variants. The identified mutation genes in this study mostly also found in other malignancies disease and two alteration genes MCM7 and STAT5 were found in disease progression of CML.Summary/Conclusion:We have sequenced the whole coding sequence of four Ph / BCR‐ABL1 positive ALLs and corresponding normal samples that allows us to overview of candidate gene in the coding regions that driving Ph‐positive ALL development and as well as enhanced our understanding of the candidate genes in diagnosis testing and prognostic prediction of adult ALLs patient.