Contribution of Chromosomal Microarrays to Precision Medicine in the Clinical Laboratory

Copy number variation (CNV) assessment is a critical component of precision medicine in almost all cancer types. For instance, copy number gain is a well described drug resistance mechanism to targeted therapies in several histologies. In patients treated with EGFR inhibitors, as an example, MET gene amplification is associated with resistance to targeted therapy; however, these patients are likely to respond to therapy. CNV assessment may also permit identification of targets for therapy. For instance, FGFR 1, 2, and 3 gene amplifications are recurring findings in urothelial carcinomas and may respond to FGFR- targeted therapies. CNV evaluation may also be of diagnostic value, as in the case of MDM2 gene amplification, which supports a diagnosis of liposarcoma.

Genomic profiling with microarray may also be valuable in hematologic malignancies. In cases of acute B lymphoblastic leukemia in which a karyotype is not attainable, a microarray genomic profile permits exclusion of hypodiploidy with endoreduplication, a known adverse prognostic factor. We have also shown the utility of microarray testing in diagnosing Burkitt-like lymphoma with 11q aberration, a recently recognized entity with aggressive behavior. Here we illustrate several examples of chromosomal microarray (CMA) testing in surgical and hematopathology applications.