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

Ryan Li, Michael F. Ochs, Sun Mi Ahn, Patrick Hennessey, Marietta Tan, Ethan Soudry, Daria A. Gaykalova, Mamoru Uemura, Mariana Brait, Chunbo Shao, William Westra, Justin Bishop, Elana J. Fertig, Joseph A. Califano

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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. Results: 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

Original languageEnglish (US)
Article numbere91263
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 27 2014
Externally publishedYes

Fingerprint

alternative splicing
squamous cell carcinoma
Alternative Splicing
Microarray Analysis
Microarrays
neck
Tumors
Genes
neoplasms
exons
Exons
Neoplasms
genes
reverse transcriptase polymerase chain reaction
Polymerase Chain Reaction
Validation Studies
Design of experiments
Epithelial Cells
Carcinoma, squamous cell of head and neck
Protein Isoforms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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

In: PLoS One, Vol. 9, No. 3, e91263, 27.03.2014.

Research output: Contribution to journalArticle

Li, R, Ochs, MF, Ahn, SM, Hennessey, P, Tan, M, Soudry, E, Gaykalova, DA, Uemura, M, Brait, M, Shao, C, Westra, W, Bishop, J, Fertig, EJ & Califano, JA 2014, 'Expression microarray analysis reveals alternative splicing of LAMA3 and DST genes in head and neck squamous cell carcinoma', PLoS One, vol. 9, no. 3, e91263. https://doi.org/10.1371/journal.pone.0091263
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. / Expression microarray analysis reveals alternative splicing of LAMA3 and DST genes in head and neck squamous cell carcinoma. In: PLoS One. 2014 ; Vol. 9, No. 3.
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