|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
DNA mismatch repair protein expression studies disclosed loss of nuclear immunostaining of MSH6 protein, pointing to the possibility of an underlying rare MSH6 variant of the Muir-Torre syndrome, not yet described in the ophthalmic literature. p16 nuclear positivity was also found in the tumor cells, indicating the possible role of high-risk human papillomavirus as an additional factor in the genesis of the tumor.
|
31557488 |
2020 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We used a combination of a tissue microarray (TMA) and whole slide staining to perform immunohistochemistry (IHC) for PMS2, MLH1, MSH2 and MSH6 and compared the results to the MMR status of the primary tumour.
|
31677289 |
2020 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Four cases had enough tissue remaining in both retained and lost MSH6 areas to perform tumor sequencing on both areas.
|
31783044 |
2020 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Tumor MMR status was determined for all patients based on reported findings for mutL homolog 1 (MLH1), postmeiotic segregation (PMS2), mutS homolog 2 (MSH2), and MSH6 immunohistochemistry; and defective MMR (dMMR) status was defined as the lack of expression of at least 1 of these proteins.
|
30561762 |
2019 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Notably, one tumor harbored a mutation in MutS homolog 6 (MSH6) that is a key mismatch repair (MMR) gene.
|
30861589 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
MSH6-negative rGBM specimens had high tumor mutational burden (TMB), but no microsatellite instability.
|
30514778 |
2019 |
|
Neoplasms
|
0.100 |
PosttranslationalModification
|
group |
BEFREE |
We previously demonstrated that in response to ROS, mismatch repair proteins MSH2 and MSH6 recruit epigenetic silencing proteins DNA methyltransferase 1 (DNMT1) and polycomb repressive complex 2 (PRC2) members to sites of DNA damage, resulting in transcriptional repression of tumor suppressor genes (TSGs).
|
30548332 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Using The Cancer Genome Atlas RNA-seq datasets with the greatest MSI-H incidence, i.e. those from colon (n = 208), stomach (n = 269), and endometrial (n = 241) cancers, we trained an algorithm to predict tumor MSI from under-expression of the mismatch repair genes MLH1, PMS2, MSH2, and MSH6 and from 10 additional genes with strong pan-cancer associations with tumor hypermutation.
|
30665466 |
2019 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Most patients (46%) had MSH6 mutations, 73% demonstrated microsatellite instability, and median tumor mutational load was 18/Mb (range, 3-165 mutations/Mb).
|
30337059 |
2019 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
However, patients with variants in MSH6 had a significant longer time to development of advanced neoplasia (advanced adenoma or CRC) than patients in the other groups.
|
31470178 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
By immunohistochemistry, the tumor was p53-wild type (DO-7 clone), diffusely positive for p16 (block positivity), and showed retained expression of PTEN, MSH2, MSH6, MLH1, and PMS2.
|
28945609 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Thereafter, to confirm the accuracy of this assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR [45 MutL homolog (MLH)1-deficient, 45 MutS protein homolog (MSH)2-deficient, and 15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set.
|
29329588 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation.
|
29750335 |
2018 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA.
|
28573495 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We found only 3 cases (0.4%) with discordant immunohistochemistry and PCR results in our own practice: 1 reflected decreased MSH-6 staining in a neoadjuvantly treated microsatellite stable tumor, 1 MLH1-deficient tumor showed diminished MLH1/PMS2 in the tumor compared with internal control, and 1 case reflected an error in the molecular laboratory.
|
29955148 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
We report the case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins).
|
28819700 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Tumor DNA microsatellite instability and immunohistochemistry testing for the expression of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2 was offered to all patients.
|
28498244 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Immunohistochemically, the tumor exhibited isolated loss of staining with the mismatch repair protein MSH6.
|
28118159 |
2017 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Genetic analysis revealed that the tumor had homozygous gene mutation of MEN1 associated with pituitary tumorigenesis and mutS homolog 6 (MSH6) gene.
|
28701629 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Ten TSGs were up-regulated (FAM123B, RB1, TP53, RUNX1, MSH2, BRCA1, BRCA2, SOX9, NPM1, and RNF43); six TSGs were down-regulated (PAX5, IZKF1, GATA3, PRDM1, TET2, and CYLD); four were associated with MSI tumors (MLH1, PTCH1, and CEBPA down-regulated and MSH6 up-regulated); and two were associated with MSS tumors (PHF6 and ASXL1 up-regulated).
|
28675510 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
All components of the tumor at both the primary and metastatic sites showed loss of MSH2 and MSH6 and retained MLH/PMS2 expression.
|
29137657 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay).
|
28418920 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001).
|
27803051 |
2017 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Targeted sequencing of 36 known or putative CRC susceptibility genes was conducted for 1231 CRC cases from five subsets: (1) Familial Colorectal Cancer Type X (<i>n</i> = 153); (2) CRC unselected by tumor immunohistochemical or microsatellite stability testing (<i>n</i> = 548); (3) young onset (age <50 years) (<i>n</i> = 333); (4) proficient mismatch repair (MMR) in cases diagnosed at ≥50 years (<i>n</i> = 68); and (5) deficient MMR CRCs with no germline mutations in MLH1, MSH2, MSH6, or PMS2 (<i>n</i> = 129).
|
28944238 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Immuno-histochemical staining of MSH2 and MSH6 shows only foci nuclear positive on the surface of the tumor with strong expression of MLH1 and PMS2 with diffuse immunoreactivity.
|
28903413 |
2017 |