Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases

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...

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Published in:Asian Pacific Journal of Cancer Prevention
Main Author: Zakaria Z.; Othman N.; Ismail A.; Kamaluddin N.R.; Esa E.; Rahman E.J.A.; Yusoff Y.M.; Fauzi F.M.; Keoh T.S.
Format: Article
Language:English
Published: Asian Pacific Organization for Cancer Prevention 2017
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019557003&doi=10.22034%2fAPJCP.2017.18.4.1169&partnerID=40&md5=afc9d03ddb5082ff198f9ab4c11ccfa7
id 2-s2.0-85019557003
spelling 2-s2.0-85019557003
Zakaria Z.; Othman N.; Ismail A.; Kamaluddin N.R.; Esa E.; Rahman E.J.A.; Yusoff Y.M.; Fauzi F.M.; Keoh T.S.
Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
2017
Asian Pacific Journal of Cancer Prevention
18
4
10.22034/APJCP.2017.18.4.1169
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019557003&doi=10.22034%2fAPJCP.2017.18.4.1169&partnerID=40&md5=afc9d03ddb5082ff198f9ab4c11ccfa7
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.
Asian Pacific Organization for Cancer Prevention
15137368
English
Article

author Zakaria Z.; Othman N.; Ismail A.; Kamaluddin N.R.; Esa E.; Rahman E.J.A.; Yusoff Y.M.; Fauzi F.M.; Keoh T.S.
spellingShingle Zakaria Z.; Othman N.; Ismail A.; Kamaluddin N.R.; Esa E.; Rahman E.J.A.; Yusoff Y.M.; Fauzi F.M.; Keoh T.S.
Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
author_facet Zakaria Z.; Othman N.; Ismail A.; Kamaluddin N.R.; Esa E.; Rahman E.J.A.; Yusoff Y.M.; Fauzi F.M.; Keoh T.S.
author_sort Zakaria Z.; Othman N.; Ismail A.; Kamaluddin N.R.; Esa E.; Rahman E.J.A.; Yusoff Y.M.; Fauzi F.M.; Keoh T.S.
title Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
title_short Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
title_full Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
title_fullStr Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
title_full_unstemmed Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
title_sort Whole-exome sequencing of ETV6/RUNX1 in four childhood acute lymphoblastic leukaemia cases
publishDate 2017
container_title Asian Pacific Journal of Cancer Prevention
container_volume 18
container_issue 4
doi_str_mv 10.22034/APJCP.2017.18.4.1169
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019557003&doi=10.22034%2fAPJCP.2017.18.4.1169&partnerID=40&md5=afc9d03ddb5082ff198f9ab4c11ccfa7
description 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.
publisher Asian Pacific Organization for Cancer Prevention
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