ArticleCancer biology & therapy2017
Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods.
Article in Cancer biology & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Predicting treatable traits for long-acting bronchodilators in patients with stable COPD.International journal of chronic obstructive pulmonary disease · 2017Trial
- Dysfunctional DNA Mismatch Repair Drives the Evolution of Gene Amplification in MTX-Resistant Human Colorectal Cancer Cells.International journal of molecular sciences · 2026Article
- Genome sequencing enhances the diagnostic yield and expands the genetic landscape of male breast cancer.Genetics in medicine open · 2025Article
- Lynch syndrome, molecular mechanisms and variant classification.British journal of cancer · 2023Review
- CRISPR Modeling and Correction of Cardiovascular Disease.Circulation research · 2022Review
- Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome.International journal of molecular medicine · 2022Article
- Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers.Nature communications · 2022Article
- PMS2 variant results in loss of ATPase activity without compromising mismatch repair.Molecular genetics & genomic medicine · 2022Article
- Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology.Cancer treatment reviews · 2022Review
- Deciphering pathogenicity of variants of uncertain significance with CRISPR-edited iPSCs.Trends in genetics : TIG · 2021Review
- TERRA Gene Expression in Gastric Cancer: Role of hTERT.Journal of gastrointestinal cancer · 2021Review
- Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation.PLoS genetics · 2020Article
- Differential expression of lung adenocarcinoma transcriptome with signature of tobacco exposure.Journal of applied genetics · 2020Article
- Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population.BMC medical genomics · 2020Article
- Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors.Advances in therapy · 2019Review
- DNA Damage Repair in Huntington's Disease and Other Neurodegenerative Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- TBL1Y: a new gene involved in syndromic hearing loss.European journal of human genetics : EJHG · 2019Article
- Illuminating the route of precision medicine and inhibitor discovery: real-time measurement of DNA repair capacity with molecular beacons.Oncotarget · 2018Article
- Determining the Pathogenicity of a Genomic Variant of Uncertain Significance Using CRISPR/Cas9 and Human-Induced Pluripotent Stem Cells.Circulation · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6, and PMS2. A major challenge for clinical diagnosis of LS is the frequent identification of variants of uncertain significance (VUS) in these genes, as it is often difficult to determine variant pathogenicity, particularly for missense variants. Generic programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON-MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS in MMR genes. We evaluated the performance of multiple predictive programs in the context of functional biologic data for 15 VUS in MLH1, MSH2, and PMS2. Using cell line models, we characterized VUS predicted to range from neutral to pathogenic on mRNA and protein expression, basal cellular viability, viability following treatment with a panel of DNA-damaging agents, and functionality in DNA damage response (DDR) signaling, benchmarking to wild-type MMR proteins. Our results suggest that the MMR gene-specific classifiers do not always align with the experimental phenotypes related to DDR. Our study highlights the importance of complementary experimental and computational assessment to develop future predictors for the assessment of VUS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.