51. Utility of microarray in the diagnosis of hematologic neoplasms with normal FISH and karyotype

Chromosome analysis and fluorescence in situ hybridization (FISH) testing are the standard techniques in diagnosis, classification, and risk assessment of hematologic neoplasms such as myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and chronic lymphocytic leukemia (CLL). Notably, the result of conventional cytogenetic testing is normal or non-informative in at least 10% of B-ALL, 50% of MDS/AML, and 15% of CLL cases, preventing accurate characterization of cancer genomic profile. Chromosomal microarray analysis (CMA) is widely used for detection of cryptic chromosomal imbalances and copy-neutral loss of heterozygosity, which are beyond the resolution of conventional cytogenetic methodologies. This study has evaluated the CMA utility and diagnostic yield in patients with an established diagnosis of either B-ALL, MDS/AML, or CLL, and negative findings of G-banding karyotype and disease-relevant FISH panel testing. During a 5-year period, karyotype, FISH and CMA were performed on 3628 samples, including 2720 cases of MDS/AML, 240 B-ALL and 668 CLL cases. At diagnosis normal karyotype and FISH were reported for 1466/2720 (54%) of patients with MDS/AML, 23/240 (9.6%) of B-ALL, and 112/668 (16.8%) of CLL cases. Using CMA, submicroscopic copy number alterations of diagnostic and prognostic significance were identified in 14.6% of MDS/AML cases, 26.1% of B-ALL, and 6.3% of CLL patients. Additionally, CMA revealed clones with large chromosomal abnormalities that were not observed among metaphase cells. Implementation of CMA in diagnosis of hematologic malignancies can significantly improve the diagnostic yield and provide data for a patient-specific risk stratification, prognostication, and therapeutic decisions.