Abstract 330: Genomic comparison of different subtypes of renal cell carcinoma using SKY, CGH

Abstract

Abstract The cytogenetic biomarkers to monitor tumor progression and treatment efficacy for renal cell carcinoma (RCC) are lacking. There are few known prognostic biomarkers that limited to tumor vascularization. In almost all sporadic clear cell RCC (ccRCC), the VHL gene in either mutated or methylated form is inactivated and often involved in cellular oxygen homeostasis. Herein, we compared different subtypes of RCC: ccRCC, chromophobe RCC (CRCC), and sarcomatoid clear cell RCC (sccRCC) in culture by using SKY and CGH. In addition, cytofluorometric analysis was performed on these tumors to give an overall immunophenotyping profile of these RCCs. By comparison of genomic characteristics of these RCC subtypes, deletion of chromosome 3p has been frequently found in sporadic ccRCC; and more complex genetic patterns of the high frequencies losses of heterozygous on chromosomes 1p, 2p, 6p, 10p, 13q, 17q, and 21q have also been documented in CRCC. However, for the sarcomatoid RCC subtype, such characteristcs have rarely been studied so far. In the current study, the genetic profile of CRCC revealed by SKY was shown: 74-84<4n> XXXX, dic(1;11)(p21;q21)×2, −3, −4, −4, der(10)(q21.1- qter), −11, −11, −18, −18, der(19)t(5;19)(q31;q?)×2, −21, −21[21]; and SCCRCC cell line showed: 40-42<2n>, X,-Y; der(2)t(2,3)(q35;q21); −3; +7,+7; der(14)(14;17)(p11;q12); −14; −15; −10; −22 [22], the data were then further confirmed by CGH for gene copy number changes of the certain specific chromosomal regions. However, for the CRCC, except loss of chromosome 21, most of genetic aberrations were different from the previous reports. On the other hand, the genetic features of current sccRCC seemed not only similar to the characteristic of ccRCC (deletion 3p), but also the genetic changes sharing the those of familial RCC (t(2;3)(q35;q21)) and papillary RCC (gain of chromosome 7 and 17, and loss of Y) documented previously. Cytofluorometric analysis revealed that there were immunophenotypic differences between CRCC and sccRCC in that surface HLA class I expression was found total loss in sccRCC, whereas CRCC expressed HLA class I abundantly on the cell surface. Furthermore, bcl-2 and URO-7 were detected in the cytoplasm of CRCC, but not in sccRCC. On the other hand, CD54 was shown on cell surface; AE3, CD44v6, Hsp70, S100-β, URO-2, URO-5, URO-9 on cell cytoplasm only observed on sccRCC. In conclusion, gain of chromosome 7 and the region harbored the oncogene c-Met were found in sccRCC, which could be related with the expression of pY1349 HGFR/c-Met associated with a high pT stage and a high metastasis rate. Therefore, it is worth to further investigate the role of c-Met and its ligand HGF in sccRCC tumorigenesis, and may help to develop clinical therapeutic strategies in sccRCC. Moreover, the immunobiological evidences clarified the significant profile of these subtypes, the information is useful on predicting the patients prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 330.