Genomic heterogeneity of translocation renal cell carcinoma Journal Article

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Authors: Malouf, G. G.; Monzon, F. A.; Couturier, J.; Molinie, V.; Escudier, B.; Camparo, P.; Su, X.; Yao, H.; Tamboli, P; Lopez-Terrada, D.; Picken, M; Garcia, M; Multani, A. S.; Pathak, S.; Wood, C. G.; Tannir, N. M.
Article Title: Genomic heterogeneity of translocation renal cell carcinoma
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 (P0.003), 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.
Journal Title: Clinical cancer research : an official journal of the American Association for Cancer Research
Volume: 19
Issue: 17
ISSN: 1078-0432; 1078-0432
Publisher: AACR  
Journal Place: United States
Date Published: 2013
Start Page: 4673
End Page: 4684
Language: eng
DOI/URL:

10.1158/1078-0432.CCR-12-3825
Notes: LR: 20150303; CI: (c)2013; GR: 5 P30 CA016672/CA/NCI NIH HHS/United States; GR: K99 CA166729/CA/NCI NIH HHS/United States; GR: P30 CA016672/CA/NCI NIH HHS/United States; GR: P30 CA046934/CA/NCI NIH HHS/United States; GR: R00 CA166729/CA/NCI NIH HHS/United States; JID: 9502500; 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors); 0 (TFEB protein, human); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); NIHMS501607; OID: NLM: NIHMS501607; OID: NLM: PMC3882157; 2013/07/01 [aheadofprint]; 2013/08/06 [aheadofprint]; ppublish