SLIT2 promoter methylation analysis in neuroblastoma, Wilms' tumour and renal cell carcinoma.
The 3p21.3 RASSF1A tumour suppressor gene (TSG) provides a paradigm for TSGs inactivated by promoter methylation rather than somatic mutations. Recently, we identified frequent promoter methylation without somatic mutations of SLIT2 in lung and breast cancers, suggesting similarities between SLIT2 and RASSF1A TSGs. Epigenetic inactivation of RASSF1A was first described in lung and breast cancers and subsequently in a wide range of human cancers including neuroblastoma, Wilms' tumour and renal cell carcinoma (RCC). These findings prompted us to investigate SLIT2 methylation in these three human cancers. We analysed 49 neuroblastomas (NBs), 37 Wilms' tumours and 48 RCC, and detected SLIT2 promoter methylation in 29% of NB, 38% of Wilms' tumours and 25% of RCC. Previously, we had demonstrated frequent RASSF1A methylation in the same tumour series and frequent CASP8 methylation in the NB and Wilms' tumour samples. However, there was no significant association between SLIT2 promoter methylation and RASSF1A or CASP8 methylation in NB and RCC. In Wilms' tumour, there was a trend for a negative association between RASSF1A and SLIT2 methylation, although this did not reach statistical significance. No associations were detected between SLIT2 promoter methylation and specific clinicopathological features in the tumours analysed. These findings implicate SLIT2 promoter methylation in the pathogenesis of both paediatric and adult cancers and suggest that further investigations of SLIT2 in other tumour types should be pursued. However, epigenetic inactivation of SLIT2 is less frequent than RASSF1A in the tumour types analysed.
Astuti
D
D
Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham B15 2TT, UK.
Da Silva
N F
NF
Dallol
A
A
Gentle
D
D
Martinsson
T
T
Kogner
P
P
Grundy
R
R
Kishida
T
T
Yao
M
M
Latif
F
F
Maher
E R
ER
D000328:Adult; D017668:Age of Onset; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007680:Kidney Neoplasms / Q000235:genetics* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000235:genetics* / Q000503:physiopathology; D000098552:Slit Homolog 2 Protein
D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000098552:Slit Homolog 2 Protein