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.
LS-related mismatch repair (MMR) genes were analyzed in 16 patients, who were forwarded to genetic testing due to strong clinical features of LS and had high-level microsatellite instability (MSI-H) in the tumor (n = 14) or unknown MSI status (n = 2).
Therefore, if sporadic tumors of a particular tissue of origin are only rarely dMMR, identifying a tumor as dMMR in a known LS family member suggests that, in that particular family, inheritance of the mutated MMR gene does predispose to that malignancy.
Interpretation of missense variants remains a major challenge for genetic diagnosis, even in well-known genes such as the DNA-mismatch repair (MMR) genes involved in Lynch syndrome.
It seems reasonable to conclude that identifying a dMMR breast cancer in a patient with known LS strongly suggests that her LS is breast cancer-predisposing.
Pathogenic variants in mismatch repair (MMR) genes (<i>MLH1, MSH2</i>, <i>MSH6</i> and <i>PMS2</i>) increase risk for Lynch syndrome and related cancers.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes.
The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome-associated endometrial cancer (LS-EC) in a prospective Chinese cohort.
Microsatellite instability (MSI), which reflects loss of DNA mismatch repair (MMR) activity, and immunohistochemistry (IHC) for MMR proteins are employed as screening examinations for Lynch syndrome (LS).
<b>Background:</b> Paired tumor-normal targeted next-generation sequencing (NGS) is primarily used to identify actionable somatic mutations, but can also detect germline variants including pathogenic germline mutations in DNA mismatch repair (MMR) genes that underlie Lynch syndrome.
Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS).
Second, when we focused on Lynch syndrome (LS) with additional selected patients, 45 were identified to carry pathogenic mutations in MMR genes, with a higher frequency found in MSH2 and MSH6.
Testicular cancer literature focuses on characterizing MSI and MMR gene expression as it relates to chemotherapy sensitivity; outcomes suggest a potential avenue to investigate its relationship to Lynch syndrome.
Many colorectal cancers (CRCs) that exhibit microsatellite instability (MSI) are not explained by MLH1 promoter methylation or germline mutations in mismatch repair (MMR) genes, which cause Lynch syndrome (LS).
Inherited mutations in DNA mismatch repair (MMR) genes, MLH1, MSH2, and MSH6, account for approximately 90% of LS, while a relatively small number of LS families segregate a PMS2 mutation.
Tumoral MMR deficiency predicted for the presence of germline MMR gene mutations in patients with HNPCC-suspicion (46/136 vs. 0/56 in patients with and without MMR deficiency, respectively).