A contemporary guide to chromosomal copy number profiling in the diagnosis of renal cell carcinoma.

Abstract The routine clinical implementation of molecular methods other than fluorescence in situ hybridization in the evaluation of renal neoplasia is currently limited, as the current standard of care primarily involves a combination of morphologic and immunophenotypic analysis of such tumors. Amongst various molecular techniques, global copy number profiling using single nucleotide polymorphism-based microarrays, colloquially referred to as SNP-arrays, is being increasingly utilized to profile renal tumors, as several subtypes have characteristic recurrent patterns of copy number alterations. Recurrent copy number alterations in common tumor types include loss of chromosome 3p in clear cell renal cell carcinoma (RCC), gain of chromosomes 7 and 17 in papillary RCC and multiple losses in chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe RCC. Such assays are being increasingly utilized in the clinical setting. Herein, we discuss some common clinical applications of such testing that includes high yield diagnostic and prognostic applications. Diagnostic utility includes evaluation of tumor types that are primarily defined by underlying copy number alterations, establishing the underlying subtype in high grade dedifferentiated (unclassified) renal tumors, as well as assessment of loss of heterozygosity, which is an important component in the workup for germline alterations in tumor suppressor genes. Universal adoption of these techniques across clinical laboratories will likely be significantly affected by variables such as cost, reimbursement, and turnaround time.