Genetics of kidney tumours

In recent years major research findings have revealed a strong correlation between the genes involved in the pathogenesis of renal tumours and the histopathological and clinical behavioural features. This new genetic information has provided the basis for the recent Heidelberg and Mayo Clinical Classifications for renal tumours. WilmsO tumour has been shown to arise from abnormalities in one of at least three genes. The first WilmsO tumour gene identified WT1, located on chromosome 11p13, encodes a zinc finger binding protein which is important in regulating the formation of the early nephron. Although the second WilmsO tumour gene, WT2, has not been formally identified it is known to be involved in the Beckwith Weideman Syndrome and in the WilmsO tumours which arise from that disease. Other WilmsO tumour genes have been implied from cytogenetic and familial data but their precise location and identification remains. In adult renal tumours there have also been considerable advances. The majority of conventional or clear cell renal carcinomas are associated with losses of chromosome 3p and mutation in the von Hippel Lindau (VHL) gene which is located on that portion of the genome. These mutations affect familial renal cancers arising as part of the VHL syndrome and the majority of sporadic renal carcinomas. There has been an energetic search for genetic abnormalities which may be involved in the progression of these tumours and data revealing the importance of chromosome 14q and other chromosomal sites have been generated. Papillary renal cancer is associated with different genetic abnormalities, in particular mutations of the c-met proto-oncogene and abnormalities of chromosome 7 with a small subgroup of familial papillary renal carcinomas showing evidence of abnormalities of the X chromosome. The less common renal carcinomas have shown cytogenetic abnormalities although the precise genes involved in their formation remain to be identified. These genetic advances have allowed a more accurate classification of renal carcinoma and WilmsO tumour and it is envisaged that they will lead to a better understanding of the biological behaviour with opportunities for therapeutic intervention in this large group of important human neoplasms.