Patrick R. Gonzales

Microarray-based comparative genomic hybridization (aCGH) allows for simultaneous high-resolution analysis of multiple genomic loci. Recently, focused aCGH platforms have emerged allowing for analysis of numerous clinically relevant chromosome loci. The purpose of our study was to evaluate the Spectral Genomics Constitutional Chip 1.0 (CC) for use in the clinical laboratory. The CC consisted of 429 BAC clones for 41 known genetic deletion/duplication syndromes, subtelomeric regions, and chromosomal backbone clones. We conducted a blinded study of 48 samples including 46 patients (one sample was run in triplicate) with previously determined constitutional chromosome anomalies and two negative controls. Patient samples included 31 microdeletions, four duplications, three derivative chromosomes, three trisomies, and five sex chromosome aneuploidies. Our results show that the CC identified the expected gains and/or losses in 46 of 48 samples. The two negative controls were considered to be normal and the three replicates of the same patient sample were concordant. Two samples yielded false-negative results; however, repeat analysis produced acceptable results for one of them. One sample ultimately had an insufficient amount of DNA precluding aCGH analysis. While promising, the results suggest that further studies are needed to reduce protocol variability and to establish standard analysis and interpretation criteria. Further, this study verifies the importance of extensive validation studies prior to clinical implementation of new clinically available methodologies.

Fluorescence in situ hybridization (FISH) remains the gold-standard clinical assay to detect genetic abnormalities in multiple myeloma (MM). However, FISH panel design, use of conventional chromosome banding analysis and reporting practices have been reported to vary among laboratories. Therefore, standardization in FISH testing and reporting practices is needed to improve report clarity and avoid misinterpretation. The recommendations in this paper represent a consensus of our Cancer Genomics Consortium Plasma Cell Neoplasm Working Group, comprising a joint panel of cytogenetic laboratory directors and clinical investigators with expertise in the diagnosis, risk stratification, and treatment of multiple myeloma. Prior to developing these consensus recommendations, we performed a full literature review and conducted a survey of 102 oncologists to assess current variations and challenges in MM cytogenetic/FISH testing and reporting. Our guidelines establish best practices for the optimization of FISH panel selection, and recommendations for standardized reporting of cytogenetic results to align with the 2025 International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) Updated Risk Stratification.