Table 1.
Syndrome | Inheritance | Gene | Estimated RCC risk | Renal tumour histological subtypes | Functional consequences of mutation |
---|---|---|---|---|---|
Von Hippel–Lindau disease | AD | VHL | 70% | Clear cell RCC | Activation of hypoxic response pathways |
Birt–Hogg–Dubé syndrome | AD | FLCN | 25% | Various, but hybrid chromophobe/oncocytic RCC typical | Activation of the mTOR pathway |
Hereditary type 1 papillary RCC | AD | MET | Increased | Papillary type 1 RCC | Activation of MET signalling pathway |
Hereditary leiomyomatosis and renal cell cancer | AD | FH | 15% | Papillary type 2 RCC | Activation of hypoxic response pathways Epigenetic changes (e.g. DNA methylation) |
Succinate dehydrogenase subunit-related RCC | AD |
SDHB
SDHD a SDHC SDHA |
Highest risk (up to 10–15% with SDHB | Various types, but specific features recognised | Activation of hypoxic response pathways Epigenetic changes (e.g. DNA methylation) |
Chromosome 3 translocations | Chromosomal | Chromosome 3 | Increased (up to 70%) | Clear cell RCC | Loss of translocated chromosome 3p and somatic mutation of VHL leads to activation of hypoxic response pathways |
PTEN hamartoma tumour syndrome | AD | PTEN | 5–35% | Mostly papillary RCC | Activation of phosphoinositide 3-kinase (PI3K) signalling pathway |
Hereditary BAP1 tumour syndrome | AD | BAP1 | Increased | Clear cell | BAP1 inactivation associated with altered chromatin architecture, DNA damage response and cell cycle regulation |
AD autosomal dominant, RCC renal cel carcinoma
aInheritance is characterised by maternal imprinting