1999 Media Guide

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

Validation tumor clinical characteristics.

<p>Validation tumor clinical characteristics.</p

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

Demographic characteristics of validation tumor and UPPP normal tissue samples.

<p>Demographic characteristics of validation 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

Validation tumor clinical characteristics.

<p>Validation tumor clinical characteristics.</p

Demographic characteristics of discovery tumor and UPPP normal tissue samples.

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

Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma

<div><p>Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.</p></div

Clinical characteristics of the cohort.

<p>Clinical characteristics of the cohort.</p

The 51 cancer genes selected for targeted or whole exon sequencing.

<p>The 51 cancer genes selected for targeted or whole exon sequencing.</p