Expression microarray analysis reveals alternative splicing of LAMA3 and DST genes in head and neck squamous cell carcinoma

Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC) is unclear. Our study queried exon-level expression to implicate splice varian...

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Bibliographic Details
Published in:PloS one 2014-03, Vol.9 (3), p.e91263-e91263
Main Authors: Li, Ryan, Ochs, Michael F, Ahn, Sun Mi, Hennessey, Patrick, Tan, Marietta, Soudry, Ethan, Gaykalova, Daria A, Uemura, Mamoru, Brait, Mariana, Shao, Chunbo, Westra, William, Bishop, Justin, Fertig, Elana J, Califano, Joseph A
Format: Article
Language:English
Subjects:
Adult
Aged
Alternative Splicing
Antigens
Biology and life sciences
Cancer genetics
Cancer therapies
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - pathology
Carrier Proteins - genetics
Comparative analysis
Cytoskeletal Proteins - genetics
DNA microarrays
Dystonin
Exons
Experimental design
Female
Gene expression
Gene Expression Profiling
Genes
Genetic engineering
Genomes
Genomics
Head
Head & neck cancer
Head and neck cancer
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - pathology
Human papillomavirus
Humans
Inspection
Laminin
Laminin - genetics
Literature reviews
Male
Medicine and Health Sciences
Middle Aged
Mutation
Neoplasm Staging
Nerve Tissue Proteins - genetics
Oligonucleotide Array Sequence Analysis
Oncology
Otolaryngology
Polymerase chain reaction
Proteins
Reproducibility of Results
RNA Isoforms
Solid tumors
Squamous cell carcinoma
Surgery
Transcription Factors - genetics
Tumor Burden
Tumor Suppressor Proteins - genetics
Tumorigenesis
Tumors
Young Adult
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Summary:Prior studies have demonstrated tumor-specific alternative splicing events in various solid tumor types. The role of alternative splicing in the development and progression of head and neck squamous cell carcinoma (HNSCC) is unclear. Our study queried exon-level expression to implicate splice variants in HNSCC tumors. We performed a comparative genome-wide analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP) tissue samples at an exon expression level. In our comparison we ranked genes based upon a novel score-the Maximum-Minimum Exon Score (MMES)--designed to predict the likelihood of an alternative splicing event occurring. We validated predicted alternative splicing events using quantitative RT-PCR on an independent cohort. After MMES scoring of 17,422 genes, the top 900 genes with the highest scores underwent additional manual inspection of expression patterns in a graphical analysis. The genes LAMA3, DST, VEGFC, SDHA, RASIP1, and TP63 were selected for further validation studies because of a high frequency of alternative splicing suggested in our graphical analysis, and literature review showing their biological relevance and known splicing patterns. We confirmed TP63 as having dominant expression of the short DeltaNp63 isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (LAMA3 and DST) validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0091263