Lynch syndrome, also known as hereditary non-polyposis colorectal cancer, characterized by predisposition to colorectal cancer and other associated cancers, is an autosomal-dominant disorder mainly caused by germline mutations in DNA mismatch repair (MMR) genes such as MLH1, MSH2, and MSH6.
Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.
A systematic search by Southern blot analysis in a cohort of 439 hereditary nonpolyposis colorectal cancer (HNPCC) families for genomic rearrangements in the main mismatch repair (MMR) genes, namely, MSH2, MLH1, MSH6, and PMS2, identified 48 genomic rearrangements causative of this inherited predisposition to colorectal cancer in 68 unrelated kindreds.
Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3.
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent hereditary form of colorectal cancer and is caused by germline mutations in mismatch repair (MMR) genes.
The frequency of constitutional mutations within the MMR genes is 1% of all newly diagnosed CRC cases and the spectrum of mutations is potentially characteristic.
In summary, SATB2 expression is a relatively specific marker of lower GI tract origin; however, loss of SATB2 expression is more commonly seen in colorectal carcinoma with MMR protein deficiency and BRAF mutation.
Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.
Previous studies have shown that MMR gene mutation carriers are at increased risk of colorectal, endometrial, and several other cancers following an initial diagnosis of colorectal cancer.
Bi-allelic germline mutations in MMR genes predispose to haematological malignancies, brain tumours, gastrointestinal tumours, polyposis and features of neurofibromatosis type 1 in early childhood.We report a brother and a sister with bi-allelic germline mutations in MSH2; a pathogenic deletion of the first 6 exons and a variant of the initiation codon (c.1A>G (p.Met1?)), whereas their phenotypes (four colorectal cancers, small bowel carcinoma and 15 adenomas at age 39 and 48, and colorectal cancer, endometrial cancer and four adenomas at age 33 and 44, respectively) are more suggestive of a mono-allelic pathogenic MMR gene mutation.
Lynch syndrome (LS) is an inherited disorder caused by a germline mutation in the DNA mismatch repair (MMR) genes and is associated with increased risk of various cancers, particularly colorectal cancer and endometrial cancer (EC).
High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2.
The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) families.
Lynch syndrome displays many curious features that cannot be accounted for by the prevailing concepts of carcinogenesis and genetics: (1) CRCs occur preferentially in the right side of the colon, whereas the majority of sporadic cases develop in the left colon; (2) the increased risk of CRC is not associated with an increased incidence of adenomatous polyps, which are necessary precancerous lesions in the development of common CRCs; (3) the tumor spectrum in Lynch syndrome is restricted to the colon and some extracolonic sites, whereas the responsible MMR genes are ubiquitously expressed; (4) the tumor risk, which is negligible during childhood, becomes significant during adulthood at the age of 25 and thereafter remains essentially constant throughout the ages.
Further research is warranted to determine whether or not dietary supplement use is associated to colorectal adenoma and colorectal cancer risk in MMR gene mutation carriers.
To evaluate our experience of adding reflex BRAF mutation analysis following mismatch repair (MMR) protein staining in the test algorithm for Lynch syndrome (LS), the most common inherited predisposition to colorectal cancer (CRC).
There was no significant difference between CRC patients and unaffected MMR gene mutation carriers for any of the SNPs studied and the Kaplan-Meier survival analysis showed no significant difference between age of diagnosis of CRC and genotype.