Adoption of Optical Genome Mapping in Clinical Cancer Cytogenetic Laboratory: A Stepwise Approach

Chromosomal abnormalities, including copy number variants (CNVs) and structural variants (SVs), are important in cancer patients, as they can inform targeted therapeutic decisions, prognostic risk stratification, and relapse prediction Therefore, the detection of CNVs and SVs in cancer patients is of great diagnostic value Routine cancer cytogenetic techniques used for detecting chromosome abnormalities include conventional chromosome analysis/karyotype, fluorescent in situ hybridization (FISH), and whole-genome chromosomal microarray assays (CMA). A karyotype can detect genome-wide CNVs and SVs at the limit of resolution of 5 -10 Mb and is commonly time-consuming. FISH is locus-specific depending on specific probes for evaluating limited CNVs and SVs in the genome. Large FISH panels containing numerous probes can detect more loci but become more expensive. CMA can detect genome-wide CNVs at a resolution that is ~ 100x more sensitive than karyotype. However, CMA cannot detect any balanced SVs such as inversions, reciprocal translocations, and insertions, or any additional balanced complex rearrangements, which may act as oncogenic driver mutations in cancers