ArticlePLoS genetics2018
Hereditary cancer genes are highly susceptible to splicing mutations.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
- The actionable transcriptome: a framework for incorporating RNA sequencing into precision oncology.Nature reviews. Clinical oncology · 2026Review
- Generation of functional noncanonical donor splice sites by +2T variants in breast cancer susceptibility genes: impact on clinical interpretation.The Journal of pathology · 2026Article
- Experimental Mis-Splicing Assessment and ACMG/AMP-Guided Classification of 47International journal of molecular sciences · 2026Article
- Unproductive alternative splicing of ATM exon 7: mapping of critical regulatory elements and identification of 34 spliceogenic variants.Journal of molecular medicine (Berlin, Germany) · 2025Article
- TP53 minigene analysis of 161 sequence changes provides evidence for role of spatial constraint and regulatory elements on variant-induced splicing impact.NPJ genomic medicine · 2025Article
- Refining the interpretation of variants of uncertain significance in hereditary cancer screening through integrated RNA sequencing.Genetics in medicine open · 2025Article
- Review
- Article
- Identifying Relationships betweenAnimals : an open access journal from MDPI · 2024Article
- RNA Panel Sequencing Is an Effective Tool to Help Classify Splice Variants for Clinical Oncogenetic Diagnosis.Human mutation · 2024Article
- Benchmarking splice variant prediction algorithms using massively parallel splicing assays.Genome biology · 2023Article
- Combining clinical and molecular characterization of CDH1: a multidisciplinary approach to reclassification of a splicing variant.Familial cancer · 2023Article
- Introns and Their Therapeutic Applications in Biomedical Researches.Iranian journal of biotechnology · 2023Review
- Transcript capture and ultradeep long-read RNA sequencing (CAPLRseq) to diagnose HNPCC/Lynch syndrome.Journal of medical genetics · 2023Article
- Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Benchmarking splice variant prediction algorithms using massively parallel splicing assays.bioRxiv : the preprint server for biology · 2023Article
- LTA4H extensively associates with mRNAs and lncRNAs indicative of its novel regulatory targets.PeerJ · 2023Article
- Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome.Genome biology · 2022Article
- Review
- Splicing Analysis of 16Cancers · 2022Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36%) of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing.
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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.