Microarray Identifies Critical Genetic Abnormalities with High Diagnostic Yield in Pediatric Neuroblastoma

Summary: Neuroblastoma (NB) is the third most common neoplasm in children. Cytogenetics abnormalities serve as crucial biomarkers for prognostication and risk stratification. This study compares the diagnostic utility of various cytogenetics methods in NB. We conducted a retrospective analysis of karyotype, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA) results of 27 NB pediatric patients referred to the UPMC Cytogenetics Laboratories between January 2023 and March 2025. The affected patients ranged in age from 4 months to 11 years (mean age: 4), including 15 females and 12 males. Karyotyping was performed on 15 of 27 cultured NB tumor specimens, by which none had chromosomal abnormalities. The remaining 12 samples did not undergo karyotype analysis, either because the analysis was not ordered, or due to poor growth or insufficient material, which is a common limitation in biopsy-derived NB samples. Interphase FISH was performed on touch preparations or uncultured cells of 25 cases, revealing MYCN amplification in 2 cases, and ploidy abnormalities (e.g., hyperdiploidy or chromosomal gains) in 15 additional cases. CMA was conducted on DNA extracted from fresh tumor tissue of 22 specimens and identified abnormalities in all the cases. The CMA findings included numerical chromosomal aberrations in 13 cases, segmental chromosomal gains/losses in 16 cases, MYCN amplification in 3 cases (including the 2 cases detected by FISH and another case did not have FISH performed), and copy-neutral loss of heterozygosity in 7 cases. Our findings underscore the superior diagnostic yield and reliability of CMA compared to karyotyping and FISH in the genetic assessment of NB. CMA demonstrated the highest detection rate and lowest failure rate, particularly for submicroscopic abnormalities beyond the resolution of traditional cytogenetics. These advantages, combined with a faster turnaround time, highlight CMA as a powerful tool for guiding risk stratification and clinical decision-making in pediatric neuroblastoma. Jeremy Feury, Qian Wang, Catherine Gestrich, Justin Kurtz, Jennifer Picarsic, and Mahmoud Aarabi