Renal cancer: Cytogenetic and molecular genetic aspects

Abstract

To date, much progress has been made in the fields of cytogenetics and molecular genetics of renal tumors. The previous and recent findings have delineated the characteristics of the various tumors, particularly the cytogenetic and molecular differences that exist between papillary and nonpapillary clear cell renal cell carcinomas (RCCs). At the same time, new cytogenetic subtypes have emerged [e.g., t(X;1)] in subtypes of RCC, while in others (e.g., Wilms tumors) several new cytogenetic abnormalities and consequent molecular involvement have been found. In addition to Wilms tumor, papillary RCC, and clear-cell RCC, cytogenetic and fluorescence in situ hybridization analyses have been performed on several other tumors of the kidney, including chromophobic carcinoma, metanephric adenoma, collecting duct carcinoma, transitional cell carcinoma, congenital mesoblastic nephroma, and malignant rhabdoid tumors of the kidney. This review is therefore intended to present a concise update on the cytogenetic and molecular data on renal tumors, focusing mainly on the clinical usefulness of the findings reported in the literature.

Protein Kinase C ζ Transactivates Hypoxia-Inducible Factor α by Promoting Its Association with p300 in Renal Cancer

“…RCC is a heterogeneous disease from both phenotypic and genetic points of view. It cannot usually be cured by conventional chemotherapy or by radiation therapy (7). Radical nephrectomy is the therapy of choice only for the initial stage; there is not yet any established therapeutic approach for the advanced metastatic stage (8).…”

“…Among the various subtypes of RCC, clear cell carcinoma is a common one (7). Most of the clear cell RCC is sporadic in nature and often develops due to the functional inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) gene product (7).…”

“…Most of the clear cell RCC is sporadic in nature and often develops due to the functional inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) gene product (7). The loss of VHL protein (pVHL) leads to increased transcription of various angiogenic growth factors such as VPF/VEGF (9, 10), transforming growth factor ␤1 (11), matrix metalloproteinase-2 (5), and so forth.…”

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

“…Distinct karyotypic aberrations also set these subtypes apart, such as loss of 3p in ccRCC compared with trisomies of 7,12,16,17, and 20 and loss of the Y chromosome in PRCC. 2,5,6 The endothelin axis comprises three endothelin peptides (ET-1, ET-2, and ET-3) and two cell-surface receptors (ET A and ET B ). Preproforms of each endothelin (PPET-1, PPET-2, and PPET-3) are cleaved to form propeptides, referred to as big ETs, which are further processed by endothelin-converting enzymes (ECEs) to generate the active 21 amino acid peptide ligands for the two receptors.…”

Tpl2 Kinase Impacts Tumor Growth and Metastasis of Clear Cell Renal Cell Carcinoma

“…RCC represents a spectrum of heterogeneous histologic and genetic subtypes (7). Among pathologic subtypes, clear cell RCC (ccRCC) accounts for approximately 80% of all RCC and shows worse clinical outcomes compared with other subtypes including papillary, chromophobe, and collecting duct cell RCC; more than 90% of metastatic RCCs are ccRCCs (8,9).…”