Data from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney

Abstract

<div>Abstract<p>Recent insights into the role of the von-Hippel Lindau (<i>VHL</i>) tumor suppressor gene in hereditary and sporadic clear-cell renal cell carcinoma (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed <i>VHL</i> as one of three genes in the 3p deletion peak, <i>CDKN2A</i> and <i>CDKN2B</i> as the only genes in the 9p deletion peak, and <i>MYC</i> as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed <i>MYC</i> as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors and thus more homogeneous overall. Sporadic tumors without evidence of biallelic <i>VHL</i> inactivation fell into two groups: one group with genomic profiles highly dissimilar to the majority of ccRCC and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of <i>VHL</i>. [Cancer Res 2009;69(11):4674–81]</p></div>