# Single Nucleotide Polymorphism Microarray Analysis Unveils Copy‐Number Abnormalities and Genetic Heterogeneity in Malaysian Childhood B‐Cell Precursor Acute Lymphoblastic Leukemia

## TL;DR

This study uses SNP microarray analysis to identify genetic variations in childhood leukemia in Malaysia, revealing new insights into the disease's genetic diversity.

## Contribution

The study provides a detailed genomic profile of BCP-ALL in Malaysian children using SNP microarray and MLPA, highlighting novel copy-number abnormalities and their implications.

## Key findings

- SNP 6.0 microarray identified 191 copy-number abnormalities in 55 patients, including hyperdiploidy, hypodiploidy, and various focal abnormalities.
- Intrachromosomal amplification of chromosome 21 (iAMP21) was not observed, indicating its rarity in the Malaysian cohort.
- MLPA confirmed abnormalities in oncogenes like CDKN2A/B, EBF1, ERG, and others, supporting the combined use of SNP and MLPA for comprehensive analysis.

## Abstract

B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) is a prevalent pediatric hematologic malignancy characterized by diverse chromosomal aberrations that significantly influence its prognosis. This study aimed to comprehensively characterize the genomic landscape of BCP‐ALL in 55 Malaysian patients with BCP‐ALL.

Single‐nucleotide polymorphism (SNP) 6.0 microarray and multiplex ligation‐dependent probe amplification were utilized to characterize and validate copy‐number abnormalities involving key oncogenes, respectively.

The SNP 6.0 microarray identified 191 copy‐number abnormalities in 55 patients, including common subtypes such as hyperdiploidy (n = 14/191, 7.3%), hypodiploidy (n = 2/191, 1.1%), and various copy‐number abnormalities such as interstitial (23.0%), terminal (17.2%), focal (37.1%), and intragenic (18.0%). Notably, intrachromosomal amplification of chromosome 21 (iAMP21) was not observed, suggesting its rarity in this cohort. Comparison with conventional cytogenetic techniques, including Trypsin‐Leishman's banding karyotyping, fluorescent in situ hybridization (FISH), and reverse transcription‐polymerase chain reaction (RT‐PCR), revealed superior resolution of the SNP 6.0 microarray in detecting submicroscopic copy‐number abnormalities. Furthermore, MLPA confirmed abnormalities in several oncogenes, including CDKN2A/B, EBF1, ERG, ETV6, IKZF1, JAK2, and PAX5.

This study demonstrates the utility of combined SNP 6.0 microarray and MLPA in providing a comprehensive and refined understanding of the genetic landscape of BCP‐ALL in the Malaysian population. This understanding may facilitate risk stratification and the development of personalized treatment strategies.

B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) is a prevalent pediatric hematologic malignancy characterized by diverse chromosomal aberrations that significantly influence its prognosis. This study aimed to comprehensively characterize the genomic landscape of childhood BCP‐ALL in a cohort of 55 Malaysian patients.