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PLoS One. 2014 Mar 27;9(3):e91263. doi: 10.1371/journal.pone.0091263. eCollection 2014.

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

Author information

1
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
2
Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Mathematics and Statistics, The College of New Jersey, Ewing, New Jersey, United States of America.
3
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
4
Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
5
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland, United States of America.

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<0.001).

CONCLUSION:

Alternative splicing events of oncologically relevant proteins occur in HNSCC. The number of genes expressing tumor-specific splice variants needs further elucidation, as does the functional significance of selective isoform expression.

PMID:
24675808
PMCID:
PMC3967989
DOI:
10.1371/journal.pone.0091263
[Indexed for MEDLINE]
Free PMC Article

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