Identification of germline mutations in DNA mismatch repair genes in colorectal cancer probands without an extensive family history can be problematic when ascribing relevance to cancer causation. We undertook a structured assessment of the disease-causing potential of sequence variants identified in a prospective, population-based study of 932 colorectal cancer patients, diagnosed at <55 years...

OBJECTIVE Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. DESIGN We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2....

Abstract Multiple large-scale genomic studies across pediatric tumors have reported an overall frequency of ~6-10% patients with constitutional pathogenic variants, but associations cancer predisposition distinct tumor types vary between zero and 100%. We analyzed sequencing DNA methylation data from 363 to explore the landscape in high-grade gliomas (pedHGG). Almost all pedHGG alterations resu...

PURPOSE: To identify the approximately 12% with inherited cancer predisposition, all men metastatic prostate (mPC) should be offered germline genetic testing. This guides treatment choices and impacts prevention in family. Limited services globally present a barrier to study tested potential solution, “mainstreaming,” where counseling testing are performed by patient’s oncologist. PATIENTS AND ...

The human genome is guarded against mutations by several DNA repair pathways. Common for all pathways, is the initiating event of detecting the DNA damage. This initial event is followed by the coordinated recruitment of various other DNA repair proteins needed for the repair. For instance, the MSH2/MSH6 complex detects DNA mismatches, while the MRN or KU70/KU80 complexes detect double strand b...

Background Hereditary Breast and Ovarian Cancer (HBOC) syndrome due to mutations in BRCA1 and BRCA2 is associated with an increase in risk for primarily breast cancer and ovarian cancer. Lynch syndrome (LS), due to mutations in MLH1, MSH2, MSH6, and PMS2 is typically associated with an increase in risk for chiefly colorectal cancer and endometrial cancer. Ovarian cancer risk is also increased i...