Detection of tetraploidization in chromophobe renal cell carcinoma: insights and pitfalls [Affymetrix OncoScan_CNV]

Chromophobic renal cell carcinomas (chRCC) typically have a hypodiploid genome, including a loss of chromosomes 1, 2, 6, 10, 13, 17 and 21, but few cases in the literature showed a gain of many chromosomes, suggesting a tetraploidy. The detection of this characteristic performed by comparative genomic hybridization (CGH-array), is very helpful for the diagnosis. To better characterize the phenomenon of tetraploidization and to explore the consequence and the difficulties of its detection, we studied a subset of 26 chRCC, including five cases of tetraploid chRCC, for which complementary analyses were performed. Our main objective was to determine whether these four cases displayed chromosomal losses typical of chRCC whitin a near-polyploid genome instead within a near-diploid one. We discuss the hazards and limitations of different molecular methods in the detection of polyploidization and its potential clinical consequences. In our study we show that this phenomenon of tetraploidization affects about 19% of chRCC and that is probably overlooked using standard molecular methods. The potential clinical consequences of this phenomenon are not identified yet. Retrospective and prospective molecular study of 26 cases of chRCC retrieved among 643 renal tumors (2012-2019). All 26 tumor samples were histologically examined and further analyzed using array-CGH (Agilent aCGH for one cases, Affymetrix aCGH for 3 cases and both technologies for 22 cases). We performed in silico manual centralization of the fluorescence ratio and array-CGH coupled to single nucleotide polymorphism (array-SNP) in the four index cases.