Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients.

Cancer Cell

ETH Zurich, Department of Computer Science, Zurich, Switzerland; Memorial Sloan Kettering Cancer Center, Computational Biology Department, New York, USA; University Hospital Zurich, Biomedical Informatics Research, Zurich, Switzerland; ETH Zurich, Department of Biology, Zurich, Switzerland; SIB Swiss Institute of Bioinformatics, Zurich, Switzerland. Electronic address:

Published: August 2018

Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A). Many tumors have thousands of alternative splicing events not detectable in normal samples; on average, we identified ≈930 exon-exon junctions ("neojunctions") in tumors not typically found in GTEx normals. From Clinical Proteomic Tumor Analysis Consortium data available for breast and ovarian tumor samples, we confirmed ≈1.7 neojunction- and ≈0.6 single nucleotide variant-derived peptides per tumor sample that are also predicted major histocompatibility complex-I binders ("putative neoantigens").

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844097PMC
http://dx.doi.org/10.1016/j.ccell.2018.07.001DOI Listing

Publication Analysis

Top Keywords

alternative splicing
24
splicing events
16
comprehensive analysis
8
analysis alternative
8
8705 patients
8
normal samples
8
alternative
6
splicing
6
tumors
4
splicing tumors
4

Similar Publications

NUMB alternative splicing and isoform specific functions in development and disease.

J Biol Chem

January 2025

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address:

The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.

View Article and Find Full Text PDF

Objectives: Many cancer cells depend on exogenous methionine for proliferation, whereas non-tumorigenic cells can divide in media supplemented with the metabolic precursor homocysteine. This phenomenon is known as methionine dependence of cancer or methionine addiction. The underlying mechanisms driving this cancer-specific metabolic addiction are poorly understood.

View Article and Find Full Text PDF

A Series of Novel Alleles of Modulating Heading and Salt Tolerance in Rice.

Plants (Basel)

January 2025

State Key Laboratory of Rice Biology and Breeding, China National Center for Rice Improvement, China National Rice Research Institute, Hangzhou 311400, China.

Rice ( L.) is a staple crop for nearly half of the global population and one of China's most extensively cultivated cereals. Heading date, a critical agronomic trait, determines the regional and seasonal adaptability of rice varieties.

View Article and Find Full Text PDF

Circular RNA Formation and Degradation Are Not Directed by Universal Pathways.

Int J Mol Sci

January 2025

Department of Rare Diseases, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.

Circular RNAs (circRNAs) are a class of unique transcripts characterized by a covalently closed loop structure, which differentiates them from conventional linear RNAs. The formation of circRNAs occurs co-transcriptionally and post-transcriptionally through a distinct type of splicing known as back-splicing, which involves the formation of a head-to-tail splice junction between a 5' splice donor and an upstream 3' splice acceptor. This process, along with exon skipping, intron retention, cryptic splice site utilization, and lariat-driven intron processing, results in the generation of three main types of circRNAs (exonic, intronic, and exonic-intronic) and their isoforms.

View Article and Find Full Text PDF

Impact of Larval Sertraline Exposure on Alternative Splicing in Neural Tissue of Adult .

Int J Mol Sci

January 2025

Immunology Laboratory (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios No. 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico.

Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat various psychiatric disorders such as depression and anxiety due to its ability to increase serotonin availability in the brain. Recent findings suggest that sertraline may also influence the expression of genes related to synaptic plasticity and neuronal signaling pathways. Alternative splicing, a process that allows a single gene to produce multiple protein isoforms, plays a crucial role in the regulation of neuronal functions and plasticity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!