Concordance of copy number abnormality detection using SNP arrays and Multiplex Ligation-dependent Probe Amplification (MLPA) in acute lymphoblastic leukaemia

• Published in: Scientific reports Vol. 10; no. 1; p. 45
• Main Authors: Bashton, Matthew, Hollis, Robin, Ryan, Sarra, Schwab, Claire J., Moppett, John, Harrison, Christine J., Moorman, Anthony V., Enshaei, Amir
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.01.2020; Nature Publishing Group
• Subjects: 631/67/2332; 692/499; Acute lymphoblastic leukemia; Algorithms; Automation; Biomarkers, Tumor - genetics; Chromosome Aberrations; Clinical trials; Cohort Studies; Copy number; Cytogenetic Analysis; Discordance; DNA Copy Number Variations; Gene Dosage; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Leukemia; multidisciplinary; Multiplex Polymerase Chain Reaction - methods; Precursor Cell Lymphoblastic Leukemia-Lymphoma - classification; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Science; Science (multidisciplinary); Segmentation; Single-nucleotide polymorphism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-56972-0

In acute lymphoblastic leukaemia, MLPA has been used in research studies to identify clinically relevant copy number abnormality (CNA) profiles. However, in diagnostic settings other techniques are often employed. We assess whether equivalent CNA profiles are called using SNP arrays, ensuring platform independence. We demonstrate concordance between SNP6.0 and MLPA CNA calling on 143 leukaemia samples from two UK trials; comparing 1,287 calls within eight genes and a region. The techniques are 99% concordant using manually augmented calling, and 98% concordant using an automated pipeline. We classify these discordant calls and examine reasons for discordance. In nine cases the circular binary segmentation (CBS) algorithm failed to detect focal abnormalities or those flanking gaps in IKZF1 probe coverage. Eight cases were discordant due to probe design differences, with focal abnormalities detectable using one technique not observable by the other. Risk classification using manually augmented array calling resulted in four out of 143 patients being assigned to a different CNA risk group and eight patients using the automated pipeline. We conclude that MLPA defined CNA profiles can be accurately mirrored by SNP6.0 or similar array platforms. Automated calling using the CBS algorithm proved successful, except for IKZF1 which should be manually inspected.