MUTYH mutations in cancer DNA were detected in 3 cases, while mutations were also found in DNA samples from normal tissues, indicating that all were germline mutations.
Age at onset of polyposis and age at surgery were 10-15 years delayed for carriers of MUTYH mutations; cancer at diagnosis was frequent, and extracolonic manifestations were diagnosed in the majority of MUTYH-positive families.
Although the number of adenomas appears to be dependent on the number of mutated MYH alleles present in a patient, little is known on the relation of this number with cancer risk.
An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing.
As the MUTYH protein interacts with the mismatch repair (MMR) system, we hypothesised that the combination of a monoallelic MUTYH mutation with an MMR gene mutation increases cancer risk.
Biallelic germline mutations in the base excision repair gene MYH have been reported in patients with multiple colorectal adenomas and cancer and in sporadic FAP patients not showing a detectable APC germline mutation.
Biallelic germline mutations in the base excision repair gene MYH have been shown to predispose to a proportion of multiple colorectal adenomas and cancer.
Further studies are necessary for the assessment of MUTYH not only in melanoma but also other cancer types with the same embryonic origin, in the context of larger arrays studies of genes involved in DNA stability or integrity.
Germinal mutations in the base excision repair (BER) gene MUTYH (MYH) have recently been described in association with predisposition to multiple colorectal adenomas and cancer.
Human H1299 cancer cell lines inducibly expressing wild-type (WT) MUTYH (type 2) or one of the 4 above-mentioned MUTYH variants were established using the piggyBac transposon vector system, enabling the genomic integration of the transposon sequence for MUTYH expression.
In one sample, the MUTYH mutation was associated with a MSH6 disease-causing mutation, suggesting that this method is helpful to identify additional cancer risk modifiers and provides a useful tool to optimize clinical issues.
In vitro analysis of Q324HMUTYH expressed in insect cells showed that it has reduced enzyme activity similar to that of the known cancer variant G382D.
MYH-associated polyposis is an inherited autosomal recessive disease, linked to biallelic germline MYH mutations, which predisposes to the development of multiple colorectal adenomas and cancer.
Polyposis associated with mutations in the gene MUTYH is an autosomal recessive syndrome characterised by the development of multiple colorectal adenomas and cancer.
Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer in materials selected for occurrence of multiple adenomas.