Discordance between germline genetic findings and abnormal tumor immunohistochemistry staining of mismatch repair proteins in individuals with suspected Lynch syndrome.

Background And Aims: Tumor immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins is often used to guide germline genetic testing and variant classification for patients with suspected Lynch syndrome. This analysis examined the spectrum of germline findings in a cohort of individuals showing abnormal tumor IHC.

Methods: We assessed individuals with reported abnormal IHC findings and referred for testing with a six-gene syndrome-specific panel (n=703).

High risk of breast cancer in women with biallelic pathogenic variants in CHEK2.

Purpose: Compared to breast cancer risk genes such as BRCA2, ATM, PALB2, and NBN, no defined phenotype is currently associated with biallelic pathogenic variants (PVs) in CHEK2. This study compared the prevalence of breast and other cancers in women with monoallelic and biallelic CHEK2 PVs.

Methods: CHEK2 PV carriers were identified through commercial hereditary cancer panel testing (09/2013-07/2019).

Increased Identification of Candidates for High-Risk Breast Cancer Screening Through Expanded Genetic Testing.

Purpose: Breast MRI screening is recommended for women with a >20% lifetime risk for breast cancer on the basis of estimates derived from risk models dependent largely on family history. Alternatively, a >20% lifetime risk can be established through genetic testing of BRCA1 and BRCA2, as well as a growing selection of other genes associated with inherited breast cancer risk. The aim of this study was to quantify the impact of testing for genes other than BRCA1/2 and the extent to which mutation carriers in these genes would have been identified as candidates for enhanced screening on the basis of family history alone.