Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, comprising approximately 25% of pediatric malignancies. Notably, chromosomal aberrations and genetic alterations play a central role in the pathogenesis of ALL, serving as critical diagnostic and prognostic markers....

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Main Authors: Ismail, Azli, Ahid, Fadly, Moi, Wong Nyuk, Kamaluddin, Nor Rizan, Esa, Ezalia, Yusoff, Yuslina Mat, Seman, Zahidah Abu, Mohammed, Muhammad Asyraff, George, Elizabeth, Isa, Asmida, Zakaria, Zubaidah
Format: Article
Language:English
Published: BioMed Central 2025
Online Access:http://psasir.upm.edu.my/id/eprint/120510/
http://psasir.upm.edu.my/id/eprint/120510/1/120510.pdf
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author Ismail, Azli
Ahid, Fadly
Moi, Wong Nyuk
Kamaluddin, Nor Rizan
Esa, Ezalia
Yusoff, Yuslina Mat
Seman, Zahidah Abu
Mohammed, Muhammad Asyraff
George, Elizabeth
Isa, Asmida
Zakaria, Zubaidah
author_facet Ismail, Azli
Ahid, Fadly
Moi, Wong Nyuk
Kamaluddin, Nor Rizan
Esa, Ezalia
Yusoff, Yuslina Mat
Seman, Zahidah Abu
Mohammed, Muhammad Asyraff
George, Elizabeth
Isa, Asmida
Zakaria, Zubaidah
author_sort Ismail, Azli
building UPM Institutional Repository
collection Online Access
description Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, comprising approximately 25% of pediatric malignancies. Notably, chromosomal aberrations and genetic alterations play a central role in the pathogenesis of ALL, serving as critical diagnostic and prognostic markers. In this study, we use array-based comparative genomic hybridization (array-CGH) to explore the landscape of copy number variations (CNVs) and variants of uncertain significance (VUS) in 67 Malaysian childhood ALL patients with normal karyotype. Results: A total of 36 pathogenic CNVs (26 gains, 10 losses) were identified in 19 (28.4%) patients which harbor genes related to the development of ALL. The genes include the MLLT3 (9p21.3), ETV6 (12p13.2), RUNX1 (21q22.12), ERG (21q22.2) and DMD (Xp21.1). On the other hand, a total of 46 variants of uncertain significance (VUS) was observed in 34 (50.7%) patients. Conclusions: Our study indicates that array-CGH is able to identify and characterize the CNVs responsible for the pathogenesis of childhood ALL. However, further studies are required to determine the pathogenic implications of VUS in the development of childhood ALL.
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spelling upm-1205102025-10-03T08:22:25Z http://psasir.upm.edu.my/id/eprint/120510/ Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH Ismail, Azli Ahid, Fadly Moi, Wong Nyuk Kamaluddin, Nor Rizan Esa, Ezalia Yusoff, Yuslina Mat Seman, Zahidah Abu Mohammed, Muhammad Asyraff George, Elizabeth Isa, Asmida Zakaria, Zubaidah Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, comprising approximately 25% of pediatric malignancies. Notably, chromosomal aberrations and genetic alterations play a central role in the pathogenesis of ALL, serving as critical diagnostic and prognostic markers. In this study, we use array-based comparative genomic hybridization (array-CGH) to explore the landscape of copy number variations (CNVs) and variants of uncertain significance (VUS) in 67 Malaysian childhood ALL patients with normal karyotype. Results: A total of 36 pathogenic CNVs (26 gains, 10 losses) were identified in 19 (28.4%) patients which harbor genes related to the development of ALL. The genes include the MLLT3 (9p21.3), ETV6 (12p13.2), RUNX1 (21q22.12), ERG (21q22.2) and DMD (Xp21.1). On the other hand, a total of 46 variants of uncertain significance (VUS) was observed in 34 (50.7%) patients. Conclusions: Our study indicates that array-CGH is able to identify and characterize the CNVs responsible for the pathogenesis of childhood ALL. However, further studies are required to determine the pathogenic implications of VUS in the development of childhood ALL. BioMed Central 2025-03-28 Article PeerReviewed text en cc_by_nc_nd_4 http://psasir.upm.edu.my/id/eprint/120510/1/120510.pdf Ismail, Azli and Ahid, Fadly and Moi, Wong Nyuk and Kamaluddin, Nor Rizan and Esa, Ezalia and Yusoff, Yuslina Mat and Seman, Zahidah Abu and Mohammed, Muhammad Asyraff and George, Elizabeth and Isa, Asmida and Zakaria, Zubaidah (2025) Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH. Molecular Cytogenetics, 18 (1). art. no. 7. pp. 1-8. ISSN 1755-8166 https://molecularcytogenetics.biomedcentral.com/articles/10.1186/s13039-025-00709-4 10.1186/s13039-025-00709-4
spellingShingle Ismail, Azli
Ahid, Fadly
Moi, Wong Nyuk
Kamaluddin, Nor Rizan
Esa, Ezalia
Yusoff, Yuslina Mat
Seman, Zahidah Abu
Mohammed, Muhammad Asyraff
George, Elizabeth
Isa, Asmida
Zakaria, Zubaidah
Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
title Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
title_full Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
title_fullStr Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
title_full_unstemmed Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
title_short Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
title_sort genomic landscape of childhood acute lymphoblastic leukemia in malaysia: insights from array-cgh
url http://psasir.upm.edu.my/id/eprint/120510/
http://psasir.upm.edu.my/id/eprint/120510/
http://psasir.upm.edu.my/id/eprint/120510/
http://psasir.upm.edu.my/id/eprint/120510/1/120510.pdf