Assessing genetic mutations in Chronic Myeloid Leukemia (CML) patients using whole exome sequencing

Chronic Myeloid leukemia (CML) is characterized by excessive accumulation of abnormal myeloid cells. Its annual occurrence is 1.0 – 1.5 per 100,000 persons. Early diagnosis may hold the key approach to treat this type of cancer. New development in Nest Generation Sequencing (NGS) shown to be useful in developing new markers for early detection of many types of cancers including breast, stomach and lung cancers. Despite presence of several markers for detection of CML, this is still room to develop new candidate genes. Here, we have employed whole exome sequencing (WES) technique and comparative bioinformatics tool to find such markers. Standard procedure was used to analyze the data. We have identified several novel SNPs and InDels variations in the genome of CML patients. However, we have only selected those InDels variations that could be easily identified by simple size fractionation following PCR reactions, with no need for follow up sequencing. After analysis of exome sequencing data from a couple of patients we have found that FAM46A, NOTCH4 and ATXN3 harbor insertion deletions (InDels) that might be involved in CML. Next, we have assessed the presence of these variations in about 30 patients and compared the results with those obtained from 20 healthy samples. Interestingly, we found that the InDels in ATXN3 gene strongly correlate with cancer status. Consequently, we propose that this variation might be useful for detection of CML at early stages.

Keywords:

CML , Whole exome sequencing , ATXN3 , early diagnosis.