Renal cell carcinoma is a commonly occurring renal malignant neoplasm in adults. Nearly 90% of renal tumors and 2% of renal malignancies are accounted for by Renal Cell Carcinomas (RCC). This cancer occurs most often in women and between age groups 55-84 yrs. Risk factors in males and females include smoking, benzene & asbestos exposure and increased BMI. Heredity could also play an important role in the development of these tumors.

The genetic basis of RCC is not well understood. Studies show that a number of genes contribute to RCC due to polymorphisms, mutations or variation in their expression. Studies on genes involved in RCC performed during the year 2009 and 2010 have been briefly listed.

Peroxisome proliferator-activated receptor gamma (PPAR?) agonists have been demonstrated to exert an inhibitory effect on cell growth in several tumor models, including clear cell renal cell carcinoma (CCRCC). PPAR? has therefore been proposed to be a potential therapeutic target. Potential mutations were analyzed by DNA sequencing of the 6 coding exons of the PPAR? gene. No mutation was found in exons 1-5. In exon 6, a silent polymorphism was detected in 14 samples (22.2%). CCRCC were found to express the PPAR?1 isoform. The expression level of PPAR? was measured by real-time quantitative PCR. In conclusion, PPAR? is expressed and functional in CCRCC, prerequisites for being a potential target for CCRCC treatment (Collet et al., 2010)

GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, it is hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN. Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. (Hong et al., 2010)

Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted. Transcription factor E3 and transcription factor EB renal cell carcinoma display different clinical behavior according to gender and age. ASPSCR1-TFE3 might be the most aggressive among the transcription factor E3 fusion genes. (Malouf et al., 2011)

Von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-a (HIF-a), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. VHL genetic alterations were identified in 43.5% (10/23) of CCRCCs. HIF-1a, HIF-2a and CAIX were up-regulated in 88.2% (15/17), 100% (17/17) and 88.2% (15/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), data suggests that other pVHL targets may be more crucial in renal carcinogenesis.(Nyhan et al., 2010)

Reference

1)Hong SB, Oh H, Valera VA, Baba M, Schmidt LS, Linehan WM. Inactivation of the FLCN Tumor Suppressor Gene Induces TFE3 Transcriptional Activity by Increasing Its Nuclear Localization. PLoS One 2010 ;5(12) 2)Collet N, Théoleyre S, Rageul J, Mottier S, Jouan F, Rioux-Leclercq N, Fergelot P, Patard JJ, Masson D, Denis MG. PPAR? is functionally expressed in clear cell renal cell carcinoma. Int J Oncol. 2010

3)Malouf GG, Camparo P, Molinié V, Dedet G, Oudard S, Schleiermacher G, Theodore C, Dutcher J, Billemont B, Bompas E, Guillot A, Boccon-Gibod L, Couturier J, Escudier B. Transcription factor E3 and transcription factor EB renal cell carcinomas: clinical features, biological behavior and prognostic factors. J Urol. 2011 Jan

4)Nyhan MJ, El Mashad SM, O'Donovan TR, Ahmad S, Collins C, Sweeney P, Rogers E, O'Sullivan GC, McKenna SL. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin. Anal Cell Pathol (Amst). 2010 Jan 1;33(3):121-32.