Project description:BACKGROUND: Cell lines have been developed for modeling cancer and cancer progression. The molecular background of these cell lines is often unknown to those using them to model disease behaviors. As molecular alterations are the ultimate drivers of cell phenotypes, having an understanding of the molecular make-up of these systems is critical for understanding the disease biology modeled. METHODS: Six immortalized normal, one immortalized dysplasia, one self-immortalized dysplasia, and two primary normal cell lines derived from oral tissues were analyzed for DNA copy number changes and changes in both mRNA and miRNA expression using SMRT-v.2 genome-wide tiling comparative genomic hybridization arrays, Agilent Whole Genome 4x44k expression arrays, and Exiqon V2.M-RT-PCR microRNA Human panels. RESULTS: DNA copy number alterations were detected in both normal and dysplastic immortalized cell lines—as well as in the single non-immortalized dysplastic cell line. These lines were found to have changes in expression of genes related to cell cycle control as well as alterations in miRNAs that are deregulated in clinical oral squamous cell carcinoma tissues. Immortal lines—whether normal or dysplastic—had increased disruption in expression relative to primary lines. All data are available as a public resource. CONCLUSIONS: Molecular profiling experiments have identified DNA,mRNA,andmiRNAalterations for a panel of normal and dysplastic oral tissue cell lines. These data are a valuable resource to those modeling diseases of the oral mucosa, and give insight into the selection of model cell lines and the interpretation of data from those lines. Total RNA from oral cancer cell lines were hybridized to Agilent 4x44k gene expression microarray
Project description:This SuperSeries is composed of the SubSeries listed below. BACKGROUND: Cell lines have been developed for modeling cancer and cancer progression. The molecular background of these cell lines is often unknown to those using them to model disease behaviors. As molecular alterations are the ultimate drivers of cell phenotypes, having an understanding of the molecular make-up of these systems is critical for understanding the disease biology modeled. METHODS: Six immortalized normal, one immortalized dysplasia, one self-immortalized dysplasia, and two primary normal cell lines derived from oral tissues were analyzed for DNA copy number changes and changes in both mRNA and miRNA expression using SMRT-v.2 genome-wide tiling comparative genomic hybridization arrays, Agilent Whole Genome 4x44k expression arrays, and Exiqon V2.M-RT-PCR microRNA Human panels. RESULTS: DNA copy number alterations were detected in both normal and dysplastic immortalized cell lines?as well as in the single non-immortalized dysplastic cell line. These lines were found to have changes in expression of genes related to cell cycle control as well as alterations in miRNAs that are deregulated in clinical oral squamous cell carcinoma tissues. Immortal lines?whether normal or dysplastic?had increased disruption in expression relative to primary lines. All data are available as a public resource. CONCLUSIONS: Molecular profiling experiments have identified DNA,mRNA,andmiRNAalterations for a panel of normal and dysplastic oral tissue cell lines. These data are a valuable resource to those modeling diseases of the oral mucosa, and give insight into the selection of model cell lines and the interpretation of data from those lines.
Project description:BACKGROUND: Cell lines have been developed for modeling cancer and cancer progression. The molecular background of these cell lines is often unknown to those using them to model disease behaviors. As molecular alterations are the ultimate drivers of cell phenotypes, having an understanding of the molecular make-up of these systems is critical for understanding the disease biology modeled. METHODS: Six immortalized normal, one immortalized dysplasia, one self-immortalized dysplasia, and two primary normal cell lines derived from oral tissues were analyzed for DNA copy number changes and changes in both mRNA and miRNA expression using SMRT-v.2 genome-wide tiling comparative genomic hybridization arrays, Agilent Whole Genome 4x44k expression arrays, and Exiqon V2.M-RT-PCR microRNA Human panels. RESULTS: DNA copy number alterations were detected in both normal and dysplastic immortalized cell lines—as well as in the single non-immortalized dysplastic cell line. These lines were found to have changes in expression of genes related to cell cycle control as well as alterations in miRNAs that are deregulated in clinical oral squamous cell carcinoma tissues. Immortal lines—whether normal or dysplastic—had increased disruption in expression relative to primary lines. All data are available as a public resource. CONCLUSIONS: Molecular profiling experiments have identified DNA,mRNA,andmiRNAalterations for a panel of normal and dysplastic oral tissue cell lines. These data are a valuable resource to those modeling diseases of the oral mucosa, and give insight into the selection of model cell lines and the interpretation of data from those lines.
Project description:We performed proteomic profiling of 88 HNSCC patients to investigate the molecular phenotype associated with engraftment. We complemented the analysis with HNSC and normal oral epithelial cell lines.
Project description:<p>Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide(1). Various chemical carcinogens (tobacco, alcohol and betel nut), human papillomavirus (HPV) infection, and genetic predisposition contribute to the etiology of HNSCC, and to the complex genetic alterations in tumor subsets that differ in prognosis and response to therapies (2).</p> <p>Recently, a comprehensive landscape of genomic and transcriptomic alterations in HNSCC tumors has emerged from The Cancer Genome Atlas (TCGA) Network (3). TCGA revealed novel and previously recognized gene and chromosomal region copy number alterations (CNAs), mutations, and expression clusters, and defined their frequency, co-occurrence, and relationship to common and rare subtypes of HPV(-) and (+) tumors that vary in prognosis. To identify cell line models for determining the functional role and therapeutic importance of these alterations, we are performing whole exome and RNA sequencing and bioinformatic analysis of an expanded panel of 15 HPV(-) and 11 HPV(+) HNSCC cell lines and primary oral keratinocytes.</p> <p>We find that the recurrent genomic alterations in cell lines are remarkably consistent with those found in more aggressive tumors, from which cell lines have traditionally been most readily adapted to culture (4). Genome-wide correlation of CN (copy number) with expression identified a suite of potential drivers or modifier genes that differ by HPV status, and are of potential biologic and therapeutic relevance. Further, our findings elucidate and validate genomic alterations underpinning numerous discoveries made with these widely-used and recently derived HNSCC lines, and provide a roadmap for their potential use as models for future studies of tumor subtypes with worse prognosis.</p> <p>References</p> <p> <ol> <li>Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.</li> <li>Van Waes C, Musbahi O. Genomics and advances towards precision medicine for head and neck squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2017;2(5):310-9.</li> <li>Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576-82.</li> <li>White JS, Weissfeld JL, Ragin CC, Rossie KM, Martin CL, Shuster M, et al. The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol. 2007;43(7):701-12.</li> </ol> </p>
Project description:Solid tumors are complex organs comprising neoplastic cells and stroma, yet cancer cell lines remain widely used to study tumor biology, biomarkers and experimental therapy. Here, we performed a fully integrative analysis of global proteomic data comparing human colorectal cancer (CRC) cell lines to primary tumors and normal tissues. We found a significant, systematic difference between cell line and tumor proteomes, with a major contribution from tumor stroma proteomes. Nevertheless, cell lines overall mirrored the proteomic differences observed between tumors and normal tissues, in particular for genetic information processing and metabolic pathways, indicating that cell lines provide a system for the study of the intrinsic molecular programs in cancer cells. Intersection of cell line data with tumor data provided insights into tumor cell specific proteome alterations driven by genomic alterations. Our integration of cell line proteogenomic data with drug sensitivity data highlights the potential of proteomic data in predicting therapeutic response. We identified representative cell lines for the proteomic subtypes of primary tumors, and linked these to drug sensitivity data to identify subtype-specific drug candidates.
Project description:The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of genetic alterations. Oral carcinogenesis is a multifactorial process involving numerous genetic changes that affect the activity of oncogenes, tumor suppressor genes and other classes of disease-related genes.Therefore, to identify the responsive genes for progression of oral dysplasia or OSCC, we here performed CGH analysis to DNA from oral dysplasia and OSCC by microdissection
Project description:We have performed gene expression microarry analysis to profile molecular alterations in normal human oral keratinocytes that are induced by EtOH and/or nicotine. Our goal is to examine molecular signatures that are dysregulated by EtOH or nicotine and define the effects of co-use of alcohol and nicotine on normal oral epithelial cells and potentially on carcinogenesis.