Mismatch repair deficiency in ovarian cancer — Molecular characteristics and clinical implications

Xiao, Xue; Melton, David W.; Gourley, Charlie

doi:10.1016/j.ygyno.2013.12.003

Cited by 89BRCA gene mutations in cancerGenetic factors in colorectal cancerOvarian cancer diagnosis and treatment

Mismatch repair deficiency in ovarian cancer — Molecular characteristics and clinical implications

Xiao, Xue, Melton, David W., Gourley, Charlie·2014·Gynecologic Oncology

DOI 10.1016/j.ygyno.2013.12.003

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Abstract

DNA mismatch repair (MMR) deficiency is associated with increased risk of developing several types of cancer and is the most common cause of hereditary ovarian cancer after BRCA1 and BRCA2 mutations. While there has been extensive investigation of MMR deficiency in colorectal cancer, MMR in ovarian cancer is relatively under-investigated. This review summarizes the mechanism of MMR, the ways in which MMR deficiency can promote carcinogenesis in general and then assesses the available studies regarding MMR deficiency in ovarian cancers with specific emphasis on implications for disease incidence and therapy. The incidence of germline MMR gene mutations in ovarian cancer is only 2% but other mechanisms of gene inactivation mean that loss of expression of one of the seven main genes (MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2) occurs in up to 29% of cases. Both mutational and expression data suggest that MMR deficiency is more common in non-serous ovarian cancer. Some studies suggest an improved survival for patients with MMR deficiency compared to historical controls but these do not account for the preponderance of non-serous tumors. A number of in vitro studies have suggested that MMR deficiency is a cause of platinum resistance. To date this has not been categorically demonstrated in the clinic. Larger studies that account for stage of presentation and immunohistochemical subtype are required to assess the effect of MMR deficiency on survival and chemosensitivity. Investigation of MMR related synthetic lethality in colorectal cancer has identified dihydrofolate reductase, DNA polymerase β and DNA polymerase γ and PTEN-induced putative kinase 1 as synthetic lethal to certain MMR defects by causing accumulation of oxidative DNA damage. These synthetic lethal targets require tested and others should be sought within the context of MMR deficient ovarian cancer in an attempt to provide novel therapeutic strategies for these patients.

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Defects in DNA repair and DNA damage response pathways can lead to human diseases such as cancer and neurodegenerative diseases.
“Defective DNA repair and DDR pathways may lead to several human diseases, such as cancer and neurodegenerative diseases [6, 33–38]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [35]
Defects in DNA repair and DDR pathways are associated with cancer and neurodegenerative diseases.
“Dysfunctions in these pathways are linked to cancer and neurodegenerative diseases [6, 33–38]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [35]

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Authors: Xiao, X., Melton, D. W., & Gourley, C.
Affiliations: Western General Hospital (GB)
Corresponding author: Gourley, Charlie
ORCID: Xiao, Xue
Gourley, Charlie
Venue: Gynecologic Oncology
Publisher: Elsevier BV
Published: 2014-02
Volume: 132
Issue: 2
Pages: 506-512
ISSN: 0090-8258 (ISSN-L)
DOI: 10.1016/j.ygyno.2013.12.003
OpenAlex: W1976342564
Cited by: 89
References: 77
Citations by year: 2026: 1 · 2025: 2 · 2024: 4 · 2023: 11 · 2022: 6 · 2021: 11 · 2020: 8 · 2019: 8 · 2018: 9 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 6
FWCI: 1.03
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gynecologic Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
Keywords: mismatch repair deficiency, ovarian cancer, hereditary ovarian cancer, MSH2, MSH6, MLH1, PMS2, platinum resistance, synthetic lethality, dihydrofolate reductase, DNA polymerase beta, DNA polymerase gamma, oxidative DNA damage, patient survival, chemosensitivity
MeSH terms: Female, Humans, Ovarian Neoplasms, DNA Mismatch Repair

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Mismatch repair deficiency in ovarian cancer — Molecular characteristics and clinical implications

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