Abstract 3427: Uncovering vulvar cancer: Integrated analysis of genomic and transcriptomic data
Authors: Lavorato-Rocha André M. , Maia Beatriz de Melo , Rodrigues Iara S. , Marchi Fabio A. , Fernandes Gabriel R. , Baiocchi Glauco , Soares Fernando A. , Rogatto Silvia R. , Sato-Kuwabara Yukie , Rocha Rafael M. 
Published: May 2015

Abstract
Vulvar squamous cell carcinoma (VSCC) is a rare gynecological cancer, representing approximately 3-5% of genital tumors. However, its incidence has risen considerably and no consistent profile of this disease was established so far. Also, little is known about the genomic abnormalities of VSCC and how they correlate with gene expression. In order to verify which are the major genomic alterations that lead to gene expression abnormalities we used integrative analysis in VSCC samples. Seventeen frozen samples of VSCC were carried out in genome-wide expression (GWE) profiling using the Agilent Whole Human Genome Microarray 60K (Agilent Technologies, Santa Clara, CA, USA) and in Array-CGH (aCGH) using the Agilent Human Genome CGH Microarray 60K (Agilent Technologies, Santa Clara, CA, USA) following the manufacturer's protocol. Data were extracted and flagged with Feature Extraction version 10.5 (Agilent Technologies, Santa Clara, CA) and the aCGH data was processed using NEXUS 6.0 (BioDiscovery, Hawthorne, CA, USA). JISTIC was used to classify genes mapped at gains and losses in genomic regions. Differentially expressed genes were identified by SAM statistical test. The CONEXIC algorithm was applied to integrate the data and in silico functional analysis were performed using Ingenuity Pathways Analysis (IPA) (Ingenuity® Systems). The aCGH analysis revealed 216 significant genomic alterations including 196 gains and 20 losses. GWE profile identified 3799 differentially expressed genes in comparison with normal tissue including 1352 up-regulated and 2447 down-regulated. The integrated analysis showed that genomic and transcriptomic results were concordant in 47 genes, in which 46 were up regulated and involved in gain of DNA copy number and only 1 gene (PLXDC2) was down-regulated and associated to genomic loss. According to IPA analysis of the top biological functions associated with the 47 genes, 3 of them were related with “tumor morphology”. Also, “cell death and survival” and “cellular function and maintenance” were included in the list of pathways disrupted by the genes selected as possible drivers of VSCC. Three significant networks could be defined comprising these genes. The first network comprised 18 of the concordant genes and was associated to functions as carbohydrate metabolism, small molecule biochemistry, cellular function and maintenance. The second network (18 genes) was related to RNA post-transcriptional modification, developmental disorder and hereditary disorder. The third network (15 genes) was associated to RNA post-transcriptional modification, gene expression and organ development. Thereby, important signaling networks were found disrupted by these genes which could influence tumor development or progression in VSCC. Therefore, these genes might be useful as a first step to identify molecular markers to improve diagnosis and therapeutic approaches for this tumor.
Citation Format: André M. Lavorato-Rocha, Beatriz de Melo Maia, Iara S. Rodrigues, Fabio A. Marchi, Gabriel R. Fernandes, Glauco Baiocchi, Fernando A. Soares, Silvia R. Rogatto, Yukie Sato-Kuwabara, Rafael M. Rocha. Uncovering vulvar cancer: Integrated analysis of genomic and transcriptomic data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3427. doi:10.1158/1538-7445.AM2014-3427