Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia Related Splice Variant of LAMA3 Associated with a Poor Prognosis

作者: Carla S. Moller-Levet , Guy N. J. Betts , Adrian L. Harris , Jarrod J. Homer , Catharine M. L. West

DOI: 10.1371/JOURNAL.PCBI.1000571

关键词: spliceExonCancer researchRNA extractionAlternative splicingGeneticsRNA splicingGeneBiologyGene expressionHead and neck squamous-cell carcinomaEcology (disciplines)Modelling and SimulationComputational Theory and MathematicsEcology, Evolution, Behavior and SystematicsMolecular biologyCellular and Molecular Neuroscience

摘要: The identification of alternatively spliced transcript variants specific to particular biological processes in tumours should increase our understanding cancer. Hypoxia is an important factor cancer biology, and associated splice may present new markers help with planning treatment. A method was developed analyse alternative splicing exon array data, using probeset multiplicity identify genes changes expression across their loci, a combination the index metric based on variation reliability weighted fold detect patterns. approach validated cancer/normal sample dataset which events had been confirmed RT-PCR. We then analysed ten head neck squamous cell carcinomas arrays identified differentially expressed five samples high versus low levels hypoxia-associated genes. analysis variant LAMA3 (Laminin alpha 3), LAMA3-A, known be involved tumour invasion progression. full-length gene (LAMA3-B) did not appear hypoxia-associated. results were qualitative In series 59 prospectively collected tumours, LAMA3-A prognostic significance whereas LAMA3-B not. This work illustrates potential for transcripts act as biomarkers disease prognosis improved specificity tissues or conditions over assays do discriminate between variants.

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