High-resolution melting (HRM) re-analysis of a polyposis patients cohort reveals previously undetected heterozygous and mosaic APC gene mutations.

Familial adenomatous polyposis is most frequently caused by pathogenic variants in either the APC gene or the MUTYH gene. The detection rate of pathogenic variants depends on the severity of the phenotype and sensitivity of the screening method, including sensitivity for mosaic variants. For 171 patients with multiple colorectal polyps without previously detectable pathogenic variant, APC was reanalyzed in leukocyte DNA by one uniform technique: high-resolution melting (HRM) analysis.

MUTYH gene variants and breast cancer in a Dutch case–control study.

The MUTYH gene is involved in base excision repair. MUTYH mutations predispose to recessively inherited colorectal polyposis and cancer. Here, we evaluate an association with breast cancer (BC), following up our previous finding of an elevated BC frequency among Dutch bi-allelic MUTYH mutation carriers.

Leiden Open Variation Database of the MUTYH gene.

The MUTYH gene encodes a DNA glycosylase involved in base excision repair (BER). Biallelic pathogenic MUTYH variants have been associated with colorectal polyposis and cancer. The pathogenicity of a few variants is beyond doubt, including c.

Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer.

Homozygous and compound heterozygous MUTYH mutations predispose for MUTYH-associated polyposis (MAP). The clinical phenotype of MAP is characterised by the multiple colorectal adenomas and colorectal carcinoma. We previously found that female MAP patients may also have an increased risk for breast cancer.

Deep sequencing to reveal new variants in pooled DNA samples.

We evaluated massive parallel sequencing and long-range PCR (LRP) for rare variant detection and allele frequency estimation in pooled DNA samples. Exons 2 to 16 of the MUTYH gene were analyzed in breast cancer patients with Illumina's (Solexa) technology. From a pool of 287 genomic DNA samples we generated a single LRP product, while the same LRP was performed on 88 individual samples and the resulting products then pooled.