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• W2741612900 abstract "As part of the Cancer Genome Atlas (TCGA) Network, our comprehensive genomic analysis of 279 head and neck squamous cell carcinomas (HNSCCs) found frequent chromosomal copy number variation (CNV) and mutations of potential biologic and therapeutic importance. This underscored an urgent need to identify cell line models that harbor genomic alterations representative of HNSCC. We performed whole exome-DNA and transcriptome RNA sequencing on 15 human papillomavirus HPV(−) and 11 HPV(+) HNSCC cell lines. HNSCC lines harbored chromosome gains (3q, 5p, 7p, 8q, 11q) and losses (3p, 5q, 8p, 9p, 18q), consistent with those found in HNSCC tumors by TCGA and previous karyotype studies. Integrative genome-wide analysis of CNV with gene expression uncovered over 1500 genes that display significant correlation between CNV and gene expression in both TCGA tumors and cell lines. Ingenuity Pathway Analysis revealed multiple genes that converge on key pathways and functions deregulated in HNSCC, including PI3K/AKT/mTOR, NF-κB, RAS/MAPK, TP53, death receptor signaling, inflammation, and differentiation. Intriguingly, 103 genes displaying significant amplification and increased expression were predominately located on chromosome 3q22-29. These genes encode components involved in the PI3K/AKT/mTOR, Hippo, TGF-beta and Wnt/beta-catenin pathways, cell cycle, translational and post-translational regulation, and mitochondrial biosynthesis. Fisher’s exact test and survival analysis showed significant co-occurrence and worse overall survival of 3q26.3 amplification and TP53 mutation in HNSCC patients from TCGA datasets; 3q26.3 encompasses 53 genes including PIK3CA, PLD1, ACTL6A and SOX2. HNSCC cell lines also harbor common mutations found in TCGA, such as TP53, FAT1 and NOTCH1, and novel and rare tumor suppressor genes, such as MYH9. Our findings suggest that these cell lines could serve as models for mechanistic studies and pharmacologic screening, and investigation of genomic and expression alterations as potential biomarkers for precision diagnosis and prognosis of HNSCC. (Supported by NIDCD/NIH intramural projects ZIA-DC-000073, ZIA-DC-000074. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. (http://biowulf.nih.gov).) Citation Format: Hui Cheng, Xinping Yang, Han Si, Anthony Saleh, Jamie Coupar, Robert L. Ferris, Wendell G. Yarbrough, Mark E. Prince, Thomas E. Carey, Carter Van Waes, Zhong Chen. Chromosome 3q22-29 amplification is linked to increased expression of multiple genes in key pathways deregulated in head and neck cancer tumors and cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4374. doi:10.1158/1538-7445.AM2017-4374" @default.
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• W2741612900 date "2017-07-01" @default.
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• W2741612900 title "Abstract 4374: Chromosome 3q22-29 amplification is linked to increased expression of multiple genes in key pathways deregulated in head and neck cancer tumors and cell lines" @default.
• W2741612900 doi "https://doi.org/10.1158/1538-7445.am2017-4374" @default.
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