Frequent RASSAF1A tumour suppresor gene promotor methylation in Wilms tumour and colorectal cancer

Kate Wagner, Wendy Cooper, Richard Grundy, Germaine Caldwell, Carolyn Jones, Roy Wadey, Dion Morton, PN Schofield, W Reik, Farida Latif, Eamonn Maher

Research output: Contribution to journalArticle

79 Citations (Scopus)


The 3p21.3 tumour suppressor gene (TSG) RASSF1A is inactivated predominantly by promoter methylation and rarely by somatic mutations. Recently we demonstrated that epigenetic inactivation of RASSF1A is frequent in both clear cell and papillary adult renal cell carcinomas (even though 3p21.3 allele loss is rare in papillary tumours). Wilms' tumour is the most common childhood kidney tumour, but relatively little is known about its molecular pathogenesis. Thus TSGs such as WT1, p16(CDKN2a) and p53 are inactivated in only a minority of cases. In view of the involvement of RASSF1A in adult renal cancers we investigated RASSF1A as a candidate Wilms' TSG. We detected RASSF1A hypermethylation in 21 of 39 (54%) primary Wilms' tumours. 3p21.3 allele loss was not detected in nine informative Wilms' tumours (five with RASSF1A methylation). In contrast to RASSF1A, only a minority (10.3%) of Wilms' tumours demonstrated p16 promoter methylation. As chromosome 3p allele loss is frequent in colorectal cancer, we proceeded to investigate RASSF1A promoter methylation in colorectal cancer and detected RASSF1A methylation in 80% (4/5) colorectal cancer cell lines and 45% (13/29) primary colorectal cancers. There was no correlation between RASSF1A and p16 methylation in colorectal cancer. We have demonstrated that RASSF1A inactivation is the most frequent genetic or epigenetic event yet reported in Wilms' tumourigenesis and that allelotyping studies may fail to identify regions containing important TSGs.
Original languageEnglish
Pages (from-to)7277-7282
Number of pages6
Issue number47
Publication statusPublished - 17 Oct 2002


  • methylation
  • Wilms' tumour
  • colorectal cancer


Dive into the research topics of 'Frequent RASSAF1A tumour suppresor gene promotor methylation in Wilms tumour and colorectal cancer'. Together they form a unique fingerprint.

Cite this