We describe a family with MSH6-dependent Lynch syndrome and familial pancreatic cancer and other tumours (gastric and endometrial), in the absence of colorectal neoplasia.
Although germline mutations of mismatch repair (MMR) genes (Lynch syndrome) are not typically associated with cholangiocarcinomas, the US Food and Drug Administration recently approved the use of pembrolizumab in patients with advanced solid tumors at all sites that show MMR deficiency or associated high microsatellite instability.
Mutations in MMR genes disrupt their mismatch repair function, cause genome instability and lead to increased risk of cancer in the mutation carriers as represented by Lynch Syndrome.
Lynch syndrome (LS) registries have been criticized for not reporting colonoscopy quality adequately.<b>Methods:</b> Prospective follow-up data from the national registry were combined with a retrospective assessment of the colonoscopy reports from Helsinki University Hospital electronic patients records in 2004-2019.<b>Results:</b> Total of 366 <i>MLH1, MSH2</i> and <i>MSH6</i> carriers underwent 1564 colorectal endoscopies (mean 4.3 per patient, range 1-10) at a single unit.
In addition, one patient with hypermutation phenotype was diagnosed as Lynch syndrome due to MLH1 mutation, suggesting the sensitivity for the treatment with immune checkpoint inhibitors.
This new case of concomitant presence of MLH1 promoter hypermethylation and MLH1 germline mutation demonstrates that the presence of MLH1 promoter hypermethylation should not rule out the diagnosis of Lynch Syndrome.
We found a novel large EPCAM-MSH2 duplication associated with LS and the presence of LOHs in regions containing numerous tumor suppressors, raising the hypothesis that these alterations could contribute to cancer susceptibility.
We found a novel large EPCAM-MSH2 duplication associated with LS and the presence of LOHs in regions containing numerous tumor suppressors, raising the hypothesis that these alterations could contribute to cancer susceptibility.
We highlight an <i>MLH1</i> variant in the colonic adenomas in an obligate Lynch syndrome carrier that resulted in PMS2 protein loss in the absence of mutations of the <i>PMS2</i> gene.
These findings suggest a large proportion of young black SA CRC patients develop via the LS pathway due to earlier age onset and predominant MSH2/6 protein loss.
This case study is of a MSH2-deficient patient with LS with metachronous urothelial and colon cancer, who received pembrolizumab treatment for 8 months.
This study demonstrates that the IHC approach for both MMR deficiency and V600EBRAF mutation detections is the most efficient approach for Lynch syndrome screening in the Italian population.