Dr. Liew Jun Mun
MBBS, MSc (Molecular Medicine), DIC
Department of Forensic Pathology
University Malaya Medical Centre
The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infected 5-10 million persons worldwide. In the United Kingdom, there are approximately 22,000 individuals who are infected with this virus and a vast majority of these individuals are asymptomatic carriers. However, in 2-6% of infected individuals, this virus causes a rare and aggressive malignancy on CD4+ T-cells. This aggressive malignancy is known as adult T-cell leukemia/lymphoma (ATL) with a low survival rate of approximately 35% after 1 year of diagnosis in its acute form.
At the Wright-Fleming Institute, St. Mary’s Hospital, London, 6 individuals presenting both before and after the diagnosis of ATL, with a follow-up range of 1.5 to 10 years were selected to our clinic. The identification of our patients was made possible through our ability to quantify and identify individual clones of HTLV-1 infected T-cells. High-throughput clonality analysis and whole exome sequencing (WES) (Illumina HiSeq2000) were performed on these samples to generate high quality reads with 90x to 100x coverage. Bioinformatics analysis was performed on these samples to identify candidate somatic mutations and for targeted sequencing to determine driver mutations in ATL from premalignant stage to full malignancy.
Our results have identified potential candidate genes in our sample population. In addition, we could also identify the diversity of dominant clonotypes by using data obtained through WES.
Through this early finding, we suggest in ATL, a sequential acquisition of mutations in the genome during disease progression accompanies the emergence of malignancy. However, further investigation is needed to determine the aetiology of these