1999 Media Guide

1999 Men\u27s Track and Field Media Guide, George Fox College

Expression Microarray Analysis Reveals Alternative Splicing of <i>LAMA3</i> and <i>DST</i> Genes in Head and Neck Squamous Cell Carcinoma

<div><p>Purpose</p><p>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.</p><p>Experimental Design</p><p>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.</p><p>Results</p><p>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 <i>LAMA3, DST, VEGFC, SDHA, RASIP1</i>, and <i>TP63</i> 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 <i>TP63</i> as having dominant expression of the short <i>DeltaNp63</i> isoform in HNSCC tumor samples, consistent with prior reports. Two of the six genes (<i>LAMA3</i> and <i>DST</i>) validated by quantitative RT-PCR for tumor-specific alternative splicing events (Student's t test, P<0.001).</p><p>Conclusion</p><p>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.</p></div

Validation tumor clinical characteristics.

<p>Validation tumor clinical characteristics.</p

Demographic characteristics of validation tumor and UPPP normal tissue samples.

<p>Demographic characteristics of validation tumor and UPPP normal tissue samples.</p

Demographic characteristics of discovery tumor and UPPP normal tissue samples.

<p>Demographic characteristics of discovery tumor and UPPP normal tissue samples.</p

Figure 1 demonstrates the experimental flow from tissue procurement to validation of tumor-specific alternative splicing events in our study.

<p>Figure 1 demonstrates the experimental flow from tissue procurement to validation of tumor-specific alternative splicing events in our study.</p

Suprabasin Is Hypomethylated and Associated with Metastasis in Salivary Adenoid Cystic Carcinoma

<div><h3>Background</h3><p>Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.</p> <h3>Principal Findings</h3><p>Here, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza-2′-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues.</p> <h3>Conclusions/Significance</h3><p>Taken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC.</p> </div

Validation tumor clinical characteristics.

<p>Validation tumor clinical characteristics.</p

Clinical and pathologic characteristics of patient populations.

*<p>Time to distant metastasis ranged from 9.1–225.7 months, with a median of 48.1 months.</p

<i>SBSN</i> is important in maintaining invasion and metastatic capability in SACC83.

<p>Matrigel invasion assay was performed with scramble control and three types of <i>SBSN</i> shRNA stable clones made from SACC83, as indicated by scramble, shRNA 1, shRNA 2, and shRNA 3. Representative photos of whole transwell membranes are pictured at 4× magnification; the inset pictures were taken at 20× magnification at randomly selected central locations. This metastasis analysis was performed in triplicate.</p