Table 1 Characteristics of the polyposis syndromes caused by biallelic germline pathogenic variants in base excision repair (BER) glycosylases.
From: MBD4-associated neoplasia syndrome: screening of cases with suggestive phenotypes
| Â | MUTYH | NTHL1 | MBD4 |
|---|---|---|---|
BER glycosylase particularities [3] | Monofunctional glycosylase. Main substrates: Adenines (A) that have been misincorporated opposite 8-oxoG/C/G. | Bifunctional: glycosylase and β-lyase. Main substrates: Tg, FapyG, 5-hC, 5-hU in dsDNA. | Monofunctional glycosylase. Main substrates: U:G and T:G, 5-hmU in CpG context (role in 5-meC demethylation: hydroxylation of 5-meC and subsequent deamination to 5-hmU, which is then removed by MBD4). |
Phenotypic characteristics of biallelic carriers | Main tumour types: Gastrointestinal (adenomatous) polyposis, CRC. Other: Ovarian cancer, bladder cancer. | Main tumour types: Gastrointestinal (adenomatous) polyposis, CRC, breast cancer, endometrial cancer. Other: Haematological malignancies, head and neck squamous cell carcinoma, bladder cancer, meningioma. | Main tumour types: Gastrointestinal (adenomatous) polyposis, AML, CRC. Other: UVM, schwannomas. |
Associated tumour mutational signatures | SBS18, SBS36 | SBS30 | SBS96 |
1: 20,000 | 1: 115,000 | 1: >1 million |
