scholarly journals DNA Mismatch Repair (MMR) Genes and Endometrial Cancer

10.5772/23995 ◽  
2011 ◽  
Author(s):  
Kenta Masuda ◽  
Kouji Banno ◽  
Megumi Yanokura ◽  
Iori Kisu ◽  
Arisa Ueki ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Dna Mismatch ◽  
Mmr Genes

Prevalence and molecular characteristics of DNA mismatch repair deficient endometrial cancer in a Japanese hospital-based population

2020 ◽  
Vol 51 (1) ◽  
pp. 60-69 ◽  
Author(s):  
Azusa Yamamoto ◽  
Tatsuro Yamaguchi ◽  
Okihide Suzuki ◽  
Tetsuya Ito ◽  
Noriyasu Chika ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Molecular Characteristics ◽  
Variant Of Uncertain Significance ◽  
Dna Mismatch ◽  
Germline Variant ◽  
Uncertain Significance ◽  
Repair Genes

Abstract Background The prevalence and molecular characteristics of defective DNA mismatch repair endometrial cancers in the Japanese population have been underexplored. Data supporting clinical management of patients with Lynch-like syndrome and germline variant of uncertain significance of mismatch repair genes are still lacking. Methods Immunohistochemistry of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary endometrial cancers in 395 women with a median age of 59 years. Genetic and/or epigenetic alterations of the mismatch repair genes were also investigated. Results Loss of expression of one or more mismatch repair proteins was observed in 68 patients (17.2%). A total of 17 out of 68 patients (25%, 4.3% of all cases) were identified as candidates for genetic testing for Lynch syndrome after excluding 51 patients with MLH1 hypermethylated cancer. Fourteen of these 17 patients subjected to genetic testing were found to have Lynch syndrome (n = 5), germline variant of uncertain significance (n = 2) or Lynch-like syndrome (n = 7). Compared with patients with Lynch syndrome, those with germline variant of uncertain significance and Lynch-like syndrome tended to demonstrate an older age at the time of endometrial cancer diagnosis (P = 0.07), less fulfillment of the revised Bethesda guidelines (P = 0.09) and lower prevalence of Lynch syndrome-associated tumors in their first-degree relatives (P = 0.01). Conclusions This study provides useful information for management in patients with DNA mismatch repair endometrial cancer. Specifically, cancer surveillance as recommended in patients with Lynch syndrome might not be necessary in patients with germline variant of uncertain significance and Lynch-like syndrome and their relatives.

Clinical characterization of DNA mismatch repair deficiency (MMR-D) in endometrial cancer (EC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 1522-1522
Author(s):  
Karen Anne Cadoo ◽  
Christina Tran ◽  
Deborah DeLair ◽  
Angela G. Arnold ◽  
Asad Ashraf ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Mismatch Repair Deficiency ◽  
Dna Mismatch ◽  
Repair Deficiency ◽  
Dna Mismatch Repair Deficiency

scholarly journals Examination of gene loss in the DNA mismatch repair pathway and its mutational consequences in a fungal phylum

2021 ◽  
Author(s):  
Megan A Phillips ◽  
Jacob L Steenwyk ◽  
Xing-Xing Shen ◽  
Antonis Rokas
Keyword(s):  
Powdery Mildew ◽  
Mismatch Repair ◽  
Gene Loss ◽  
Dna Mismatch Repair ◽  
Gc Content ◽  
Mutational Bias ◽  
Sequence Evolution ◽  
Loss Of Function ◽  
Dna Mismatch ◽  
Mmr Genes

AbstractThe DNA mismatch repair (MMR) pathway corrects mismatched bases produced during DNA replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss of function in one or a few MMR genes can lead to increased mutation rates and microsatellite instability, as seen in some human cancers. While loss of MMR genes has been documented in the context of human disease and in hypermutant strains of pathogens, examples of entire species and species lineages that have experienced substantial MMR gene loss are lacking. We examined the genomes of 1,107 species in the fungal phylum Ascomycota for the presence of 52 genes known to be involved in the MMR pathway of fungi. We found that the median ascomycete genome contained 49 / 52 MMR genes. In contrast, four closely related species of obligate plant parasites from the powdery mildew genera Erysiphe and Blumeria, have lost between 6 and 22 MMR genes, including MLH3, EXO1, and DPB11. The lost genes span MMR functions, include genes that are conserved in all other ascomycetes, and loss of function of any of these genes alone has been previously linked to increased mutation rate. Consistent with the hypothesis that loss of these genes impairs MMR pathway function, we found that powdery mildew genomes with high levels of MMR gene loss exhibit increased numbers of monomer repeats, longer microsatellites, accelerated sequence evolution, elevated mutational bias in the A|T direction, and decreased GC content. These results identify a striking example of macroevolutionary loss of multiple MMR pathway genes in a eukaryotic lineage, even though the mutational outcomes of these losses appear to resemble those associated with detrimental MMR dysfunction in other organisms.

A phase II trial of durvalumab (Medi 4736) in advanced endometrial cancer: PHAEDRA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5614-TPS5614 ◽  
Author(s):  
Yoland Catherine Antill ◽  
Martin R. Stockler ◽  
Peey Sei Kok ◽  
Kristy Pamela Robledo ◽  
Kim Gillies ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Unmet Need ◽  
Tumour Response ◽  
Survival Duration ◽  
Genetic Characteristics ◽  
Objective Tumour Response ◽  
Dna Mismatch

TPS5614 Background: Advanced endometrial cancer (EC) progressing after 1 or more lines of chemotherapy is an area of unmet need with objective tumour response rates to subsequent lines of chemotherapy of ≤20%. DNA mismatch repair (MMR) deficiency, seen in approximately 15% of EC, is associated with a high mutational load and in addition, up to 90% of ECs are reported to have PDL1/ PD1 expressions. These factors make immune check point inhibition an ideal target for treatment. Methods: DESIGN: Multicentre phase 2 trial in two cohorts. ELIGIBILITY: Advanced, unresectable endometrial cancer that is either MMR-proficient and progressing after 1-3 lines of chemotherapy, or MMR-deficient and progressing after 0-3 lines of chemotherapy. ENDPOINTS: Objective tumour response rate (OTRR) according to iRECIST (primary) and RECIST 1.1, disease control rates at 16 and 24 weeks, progression free survival, overall survival, duration of OTR and DC, adverse events, health related quality of life. Tertiary correlative objectives: Associations between immunologic (including PD-L1), DNA mismatch repair (MMR) and other genetic characteristics with clinical outcomes; and family history of cancer and referral to familial cancer services. INTERVENTION: Durvalumab 1500 mg intravenously every 28 days until disease progression or prohibitive toxicity. STATISTICS: Total of 70 participants in two cohorts (35 each) will have 90% power to distinguish a difference in observed OTRR of ≥20% versus ≤5% (uninteresting rate) using Simon’s 2-stage minimax design with 10% type 1 error rate and allowing 10% ineligibility and missing data. Durvalumab will be considered worthy of pursuit if 4 or more OTR are observed in the first 32 participants in each cohort (OTRR ≥12.5%). BIOSPECIMENS: Tumour tissue and serial bloods (5 time points) will be collected for translational research. PHAEDRA is an investigator-initiated, cooperative-group trial led by ANZGOG, in collaboration with NHMRC Clinical Trials Centre, University of Sydney. Australian New Zealand Clinical Trials Registry: Clinical trial information: ACTRN12617000106336.

scholarly journals Epimutation in DNA Mismatch Repair (MMR) Genes

10.5772/53812 ◽  
2013 ◽  
Author(s):  
Kouji Banno ◽  
Iori Kisu ◽  
Megumi Yanokura ◽  
Yuya Nogami ◽  
Kiyoko Umene ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Dna Mismatch ◽  
Mmr Genes
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