APC Splicing Mutations Leading to In-Frame Exon 12 or Exon 13 Skipping Are Rare Events in FAP Pathogenesis and Define the Clinical Outcome

Disciglio, Vittoria; Forte, Giovanna; Fasano, Candida; Sanese, Paola; Signorile, Martina Lepore; Marco, Katia De; Grossi, Valentina; Cariola, Filomena; Simone, Cristiano

doi:10.3390/genes12030353

Cited by 3 publications

(2 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, β-catenin levels are increased, and the expression of growth-promoting genes can be increased through downstream T-cell transcription factor (Tcf) pathways. Mutations inducing exons 12 and 13 skipping resulted in the loss of armadillo functional domains without disrupting the open reading frame, and patients carrying this variant showed a less severe FAP phenotype than patients with truncation mutations 143 .…”

Section: Wnt/β-catenin Pathwaymentioning

confidence: 98%

The implications of alternative pre-mRNA splicing in cell signal transduction

2023

View full text Add to dashboard Cite

Cells produce multiple mRNAs through alternative splicing, which ensures proteome diversity. Because most human genes undergo alternative splicing, key components of signal transduction pathways are no exception. Cells regulate various signal transduction pathways, including those associated with cell proliferation, development, differentiation, migration, and apoptosis. Since proteins produced through alternative splicing can exhibit diverse biological functions, splicing regulatory mechanisms affect all signal transduction pathways. Studies have demonstrated that proteins generated by the selective combination of exons encoding important domains can enhance or attenuate signal transduction and can stably and precisely regulate various signal transduction pathways. However, aberrant splicing regulation via genetic mutation or abnormal expression of splicing factors negatively affects signal transduction pathways and is associated with the onset and progression of various diseases, including cancer. In this review, we describe the effects of alternative splicing regulation on major signal transduction pathways and highlight the significance of alternative splicing.

show abstract

Section: Wnt/β-catenin Pathwaymentioning

confidence: 98%

The implications of alternative pre-mRNA splicing in cell signal transduction

2023

View full text Add to dashboard Cite

show abstract

“…It was also found that mutations in the APC led to skipping of exons or appearance of new sites of splicing [ 272 , 273 , 274 ]. Recent studies also revealed numerous novel splice sites creating mutations in cancer cells.…”

Section: Defects In Splicing and Cancermentioning

confidence: 99%

Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors

Kretova

Selicky

Cipakova

et al. 2023

Life

View full text Add to dashboard Cite

Pre-mRNA splicing is a process used by eukaryotic cells to generate messenger RNAs that can be translated into proteins. During splicing, the non-coding regions of the RNAs (introns) are removed from pre-mRNAs and the coding regions (exons) are joined together, resulting in mature mRNAs. The particular steps of splicing are executed by the multimegadalton complex called a spliceosome. This complex is composed of small nuclear ribonucleoproteins, various splicing factors, and other regulatory and auxiliary proteins. In recent years, various post-translational modifications of splicing factors have been shown to contribute significantly to regulation of processes involved in pre-mRNA splicing. In this review, we provide an overview of the most important post-translational modifications of splicing factors that are indispensable for their normal function during pre-mRNA splicing (i.e., phosphorylation, acetylation, methylation, ubiquitination and sumoylation). Moreover, we also discuss how the defects in regulation of splicing factors are related to the development of cancer.

show abstract

Clinical Assessment and Genetic Testing for Hereditary Polyposis Syndromes in an Italian Cohort of Patients with Colorectal Polyps

Fasano,

Cariola,

Forte

et al. 2024

Cancers

View full text Add to dashboard Cite

Background: Hereditary polyposis syndromes are clinically and genetically heterogeneous conditions associated with increased colorectal cancer risk. They are classified based on polyp histology, inheritance mode, causal gene, and colonic and extracolonic manifestations. Their diagnosis is challenging due to overlapping and heterogeneous clinical presentations. Methods: A multigene next-generation sequencing panel was used to screen 75 index cases with colorectal polyps and a personal/family history of cancer for key hereditary polyposis-associated genes (APC, BMPR1A, MUTYH, PTEN, SMAD4, and STK11) in order to identify germline genetic variants. Results: In the screened index cases, we found 14 pathogenic variants involving APC, MUTYH, SMAD4, and STK11 and 6 variants of uncertain significance involving APC, BMPR1A, and SMAD4. In this cohort, four patients not fulfilling the recommended eligibility criteria of current National Comprehensive Cancer Network (NCCN) guidelines for genetic testing were molecularly diagnosed with a hereditary polyposis syndrome. Conclusions: Our findings indicate that stringent NCCN eligibility criteria for molecular screening may lead to missing some of the patients affected by hereditary polyposis syndromes. This highlights the need for a careful evaluation of patients’ clinical manifestations, polyp number, age of polyp onset, and family history to select appropriate candidates for molecular diagnosis of these conditions.

show abstract

APC Splicing Mutations Leading to In-Frame Exon 12 or Exon 13 Skipping Are Rare Events in FAP Pathogenesis and Define the Clinical Outcome

Cited by 3 publications

References 108 publications

The implications of alternative pre-mRNA splicing in cell signal transduction

The implications of alternative pre-mRNA splicing in cell signal transduction

Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors

Clinical Assessment and Genetic Testing for Hereditary Polyposis Syndromes in an Italian Cohort of Patients with Colorectal Polyps

Contact Info

Product

Resources

About