TY - JOUR ID - 46277 TI - Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Zakaria, Zubaidah AU - Othman, Norodiyah AU - Ismail, Azli AU - Kamaluddin, Nor Rizan AU - Esa, Ezalia AU - Abdul Rahman, Eni Juraida AU - Mat Yusoff, Yuslina AU - Mohd Fauzi, Fazlin AU - Sew Keoh, Ten AD - Haematology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur 50588, Malaysia. AD - Paediatrics Institute, General Hospital Kuala Lumpur, Kuala Lumpur 50586, Malaysia. AD - Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Selangor 42300, Malaysia. Y1 - 2017 PY - 2017 VL - 18 IS - 4 SP - 1169 EP - 1175 KW - Whole-exome sequencing KW - ETV6/RUNX1 fusion gene KW - Acute Lymphoblastic Leukaemia KW - secondary genetic alteration DO - 10.22034/APJCP.2017.18.4.1169 N2 -   Background: ETV6/RUNX1 gene fusion is the most frequently seen chromosomal abnormality in childhood acute lymphobastic leukamia (ALL). However, additional genetic changes are known to be required for the development of this type of leukaemia. Therefore, we here aimed to assess the somatic mutational profile of four ALL cases carrying the ETV6/RUNX1 fusion gene using whole-exome sequencing. Methods: DNA was isolated from bone marrow samples using a QIAmp DNA Blood Mini kit and subsequently sequenced using the Illumina MiSeq system. Results: We identified 12,960 to17,601 mutations in each sample, with a total of 16,466 somatic mutations in total. Some 15,533 variants were single nucleotide polymorphisms (SNPs), 129 were substitutions, 415 were insertions and 389 were deletions. When taking into account the coding region and protein impact, 1,875 variants were synonymous and 1,956 were non-synonymous SNPs. Among non-synonymous SNPs, 1,862 were missense, 13 nonsense, 35 frameshifts, 11 nonstop, 3 misstart, 15 splices disrupt and 17 in-frame indels. A total of 86 variants were located in leukaemia-related genes of which 32 variants were located in the coding regions of GLI2, SP140, GATA2, SMAD5, KMT2C, CDH17, CDX2, FLT3, PML and MOV10L1. Conclusions: Detection and identification of secondary genetic alterations are important in identifying new therapeutic targets and developing rationally designed treatment regimens with less toxicity in ALL patients. UR - https://journal.waocp.org/article_46277.html L1 - https://journal.waocp.org/article_46277_7e5612288b7ee402563322927e553a3c.pdf ER -