PDF file - 86K, Supplementary Table 1. Clinicopathologic characteristics of patients with confirmed Translocation RCC Supplementary Table 2: Clinicopathological features of TFE3 overexpressing renal cell carcinoma with no TFE3 translocation identified. Supplementary Table 3: List of upstream regulators predicted to be activated or inhibited in two cases of translocation renal cell carcinoma with concomitant 17q gain and 17p loss as compared to two cases with balanced karyotype.
ARTICLE ABSTRACT
Purpose: Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity.Experimental Design: Cytogenomic analysis was conducted with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and four cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was conducted on 27 cases using pyrosequencing.Results: tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in seven tumors (44%), followed by a 9p loss in six cases (37%). Less frequent were losses of 3p and 17p in five cases (31%) each. Patients with 17q gain were older (P = 0.0006), displayed more genetic alterations (P < 0.003), and had a worse outcome (P = 0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large-scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell line–based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared with tumors from young patients (71.1% vs. 76.7%; P = 0.02).Conclusions: Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology. Clin Cancer Res; 19(17); 4673–84. ©2013 AACR.
