The results of in vitro and in vivo experiments indicated that MLH1, together with low levels of Top1, contributed to colon cancer resistance to irinotecan.
We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer.
The aim of the study was to compare the distribution of MLH1 -93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects.
We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer.
In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1).
In blinded specimens and colon cancer cell lines with defined mutations, ColoSeq correctly identified 28/28 (100%) pathogenic mutations in MLH1, MSH2, MSH6, PMS2, EPCAM, APC, and MUTYH, including single nucleotide variants (SNVs), small insertions and deletions, and large copy number variants.
We describe a patient with a Homo sapiens mutL homolog 1 (MLH1)-associated Lynch syndrome with previous diagnoses of two distinct primary cancers: a sigmoid colon cancer at the age of 39 years, and a right colon cancer at the age of 50 years.
We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon Cancer Family Registry.
Risk of metachronous CRC was estimated for 382 MMR gene mutation carriers (172 MLH1, 167 MSH2, 23 MSH6 and 20 PMS2) from the Colon Cancer Family Registry, who had surgery for their first colon cancer, using retrospective cohort analysis.
In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer.
Statistically significant interactions were observed between: MLH1 -93G>A and smoking (MSI-negative colon cancer only, p value interaction: 0.005); and MLH1Ile219Val and Western diet (p value interaction: 0.03).
Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L.
We previously identified a novel genomic instability phenotype of multiple reciprocal chromosomal translocations in a MLH1-defective, microsatellite unstable (MSI) colon cancer cell line (HCA7) and, further, showed that it was unlikely to be directly caused by the mismatch repair (MMR) defect in this cell line.
Here we report the first proven de novo germ line mutation in MLH1 (c.666dupA) identified in a 31-year-old colorectal cancer patient with the alteration being present in a heterozygous state in all three germ layers and homozygously in his colon cancer.