Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH
Abstract 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 m...
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BMC
2025-03-01
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| Series: | Molecular Cytogenetics |
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| Online Access: | https://doi.org/10.1186/s13039-025-00709-4 |
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| author | Azli Ismail Fadly Ahid Wong Nyuk Moi Nor Rizan Kamaluddin Ezalia Esa Yuslina Mat Yusoff Zahidah Abu Seman Muhammad Asyraff Mohammed Elizabeth George Asmida Isa Zubaidah Zakaria |
| author_facet | Azli Ismail Fadly Ahid Wong Nyuk Moi Nor Rizan Kamaluddin Ezalia Esa Yuslina Mat Yusoff Zahidah Abu Seman Muhammad Asyraff Mohammed Elizabeth George Asmida Isa Zubaidah Zakaria |
| author_sort | Azli Ismail |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a96a630c819945229dfdf9d9e318d5a2 |
| institution | Kabale University |
| issn | 1755-8166 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Molecular Cytogenetics |
| spelling | doaj-art-a96a630c819945229dfdf9d9e318d5a22025-08-20T03:40:47ZengBMCMolecular Cytogenetics1755-81662025-03-011811810.1186/s13039-025-00709-4Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGHAzli Ismail0Fadly Ahid1Wong Nyuk Moi2Nor Rizan Kamaluddin3Ezalia Esa4Yuslina Mat Yusoff5Zahidah Abu Seman6Muhammad Asyraff Mohammed7Elizabeth George8Asmida Isa9Zubaidah Zakaria10Hematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health MalaysiaCentre for Medical Laboratory Technology Studies, Faculty of Health Sciences, Universiti Teknologi MARAMedical Laboratory Technology College, Ministry of Health MalaysiaHematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health MalaysiaHematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health MalaysiaHematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health MalaysiaHematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health MalaysiaHematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health MalaysiaFaculty of Medical and Health Sciences, Universiti Putra MalaysiaDepartment of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains MalaysiaPremier Integrated Labs, Pantai Hospital AmpangAbstract 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.https://doi.org/10.1186/s13039-025-00709-4Array-based comparative genomic hybridizationChildhood acute lymphoblastic leukemiaCopy number variationsVariants of uncertain significance |
| spellingShingle | Azli Ismail Fadly Ahid Wong Nyuk Moi Nor Rizan Kamaluddin Ezalia Esa Yuslina Mat Yusoff Zahidah Abu Seman Muhammad Asyraff Mohammed Elizabeth George Asmida Isa Zubaidah Zakaria Genomic landscape of childhood acute lymphoblastic leukemia in Malaysia: insights from array-CGH Molecular Cytogenetics Array-based comparative genomic hybridization Childhood acute lymphoblastic leukemia Copy number variations Variants of uncertain significance |
| 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 |
| topic | Array-based comparative genomic hybridization Childhood acute lymphoblastic leukemia Copy number variations Variants of uncertain significance |
| url | https://doi.org/10.1186/s13039-025-00709-4 |
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