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.

Nyckelord

Adult

Age of Onset

Carcinoma

Renal Cell

genetics

physiopathology

Child

DNA Methylation

DNA

Neoplasm

genetics

Epigenesis

Genetic

Humans

Intercellular Signaling Peptides and Proteins

Kidney Neoplasms

genetics

physiopathology

Nerve Tissue Proteins

genetics

Neuroblastoma

genetics

physiopathology

Promoter Regions (Genetics)

Reverse Transcriptase Polymerase Chain Reaction

Wilms Tumor

genetics

physiopathology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)