|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The mutations of MLH1 V384D (15.7%), R217C (4.1%), and I219V (5.2%) were common in this cancer.
|
27487738 |
2016 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The inactivation of an MMR gene (MSH2, MSH6, MLH1, or PMS2) with an inherited mutation causes Lynch syndrome (LS), a dominant susceptibility to cancer.
|
22581703 |
2012 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The mutated MLH1 P648S protein was found to be unstable but still functional in mismatch repair, suggesting that the cancer susceptibility in the family and possibly also the mild disease phenotype in the homozygous individual are linked to shortage of the functional protein.
|
15139004 |
2004 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Cancer susceptibility genes have been classified as "gatekeepers" (e.g.RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1).
|
11205230 |
2001 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Germline mutations in two human mismatch repair (MMR) genes, hMSH2 and hMLH1, appear to account for approximately 70% of the common cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC).
|
10037723 |
1999 |
|
Primary malignant neoplasm
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC.
|
29701748 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
PosttranslationalModification
|
group |
BEFREE |
MLH1 methylation was also prognostic, particularly in large cell cancer (P=0.006).
|
18594535 |
2008 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Families with known germline mutations of hMLH1 (n = 39) and hMSH2 (n = 45) were extracted from the Dutch HNPCC cancer registry.
|
15937084 |
2005 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations.
|
17116713 |
2006 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
We consider the possibility that loss of apoptosis as a result of hMSH2 or hMLH1 deficiency may be an additional factor in cancer predisposition in HNPCC.
|
10397236 |
1999 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system.
|
7713503 |
1994 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Reduced PTEN protein expression was detected in 7 of 46 cases (15.21%): 5 were clinically classified as stage IV, and the other 2 presented both cancer and hypermethylated hMLH1.
|
12402310 |
2002 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Of these 77 individuals with cancer (19 fallopian, 8 gallbladder, 17 biliary, 17 pancreatic, 11 urothelial, 5 small intestinal), 39 (50.6%) had at least one first degree relative with cancer (excluding lung and skin); two conformed to Bethesda HNPCC criteria.
|
14574163 |
2003 |
|
Primary malignant neoplasm
|
0.100 |
AlteredExpression
|
group |
BEFREE |
A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6.
|
29164703 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
We evaluated the role of MLH1 K618A in predisposition to cancer by genotyping 1512 control subjects to assess its frequency in the general population.
|
22426235 |
2012 |
|
Primary malignant neoplasm
|
0.100 |
PosttranslationalModification
|
group |
BEFREE |
Bisulfite analysis suggests that the mechanisms of hMLH1 silencing may depend on CpG density rather than site-specific methylation.Cancer 2003;98:1540-6.
|
14508843 |
2003 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
To determine the role played by MLH1 and MSH2 missense variants in cancer susceptibility, we have investigated the following genetic and biological characteristics associated with six MLH1 and four MSH2 missense changes identified in Italian hereditary nonpolyposis colorectal cancer (HNPCC) families: co-segregation with disease phenotype and/or bonafide pathogenetic mutations; presence of the variant in healthy control subjects; evolutionary conservation of the involved aminoacid and type of aminoacid change; and presence/absence of microsatellite instability (MSI) in tumour DNA.
|
10573010 |
2000 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In this review, we discuss the adverse consequences suffered by a cell when DNA repair genes such as the DNA mismatch repair gene hMLH1, the DNA alkyl-repair gene O(6)-methylguanine-DNA methyltransferase, the familial breast cancer gene BRCA1 and the Werner syndrome gene WRN become epigenetically silenced in human cancer.
|
17412712 |
2007 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
Loss of hMLH1 in MSI-H but not in MSI-L lesions showing dysplasia or cancer was significant (p<0.001, Fisher's exact test).
|
10861263 |
2000 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Lynch syndrome (hereditary non-polyposis colorectal cancer; HNPCC) is an autosomal dominant cancer predisposition syndrome with high penetrance.
|
23255519 |
2013 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Germline mutations in mismatch repair genes, predominantly MSH2 and MLH1, have been found to underlie the Lynch syndrome (also called hereditary non-polyposis colorectal cancer, HNPCC), a hereditary predisposition for cancer.
|
16821093 |
2006 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
These findings are of particular clinical and genetic significance because HNPCC lacks premonitory signs of cancer risk.
|
4016686 |
1985 |
|
Primary malignant neoplasm
|
0.100 |
PosttranslationalModification
|
group |
BEFREE |
In summary, the epigenetic repression of DNA damage repair genes due to promoter hypermethylation of MLH1 and MSH2 and inefficient recruitment of MMR complex at the site of DNA damage owing to the reduced level of H3K36me3 impairs the mismatch repair pathway that might render the arsenic-exposed individuals more susceptible towards DNA damage and associated cancer risk.
|
29499398 |
2018 |
|
Primary malignant neoplasm
|
0.100 |
Biomarker
|
group |
BEFREE |
MLH1-deficient patients who are young or have a positive family history of cancer should be referred for genetic testing and counselling, whereas MSH2-deficient patients should be counselled in the same way as patients with HNPCC.
|
17440950 |
2007 |
|
Primary malignant neoplasm
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The novel germline mutation of the hMLH1 gene in a case of suspected hereditary non-polyposis colorectal cancer (HNPCC) in a patient with no family history of cancer.
|
15466831 |
2004 |