HD-SNP Microarray Analysis of the Study 9 High Risk ALL Patients—Increased Yield of Important Prognostic Information

Background: There are limitations in the characterisation of genome-wide aberrations in acute lymphoblastic leukaemia (ALL) using current methodologies such as karyotype, extensive FISH panels and RT-PCR. This is often due to poor metaphase morphology, and the specificity of FISH and RT-PCR panels. High density SNP microarrays offer improved detection of CNV gains and losses as well as copy neutral loss of heterozygosity (cnLOH) not detectable using conventional methods in ALL. Aims: We aim to identify genomic changes using HD-SNP microarray in a cohort of high risk ALL subjects enrolled. We also aim to assess the value of this technology in a clinical setting to refine risk stratification. Methods: DNA was extracted from 23 high risk ALL patients with whole bone marrow (BM) taken at diagnosis and/or at relapse. SNP-microarray analysis was performed using the Affymetrix HD platform and analysed using ChAS software [Affymetrix]. Results were compared to karyotype and FISH results. Results: Analysis by HD SNP-microarray increased detection rate of abnormalities to 100% of the cohort compared to 57% (13/23) for karyotyping and 48% (11/23) for FISH. Important microdeletions, including IKZF1, PTEN, CDKN2A and the fusion forming microdeletions of STIL-TAL1 and CSF2RA-IL3RA were identified by HD SNP-microarray but not detected by karyotype or FISH. Also, numerous regions of cn-LOH were also observed. Conclusions: SNP-microarray analysis substantially increases and improves the detection of prognostic genomic aberrations in paediatric ALL. This technology complements the current clinical and laboratory techniques (including MRD) for risk stratification and treatment of ALL at diagnosis.