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Verhaak, Roel

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Verhaak

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Roel

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Verhaak, Roel

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2008 - 20092

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Author's Publications: search.filters.isAuthorOfPublication.2989157b-c4ea-45ef-82f4-df89c6c9d3ec

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    SNPExpress: Integrated Visualization of Genome-wide Genotypes, Copy Numbers and Gene Expression Levels

    (BioMed Central, 2008) Sanders, Mathijs A; Verhaak, Roel; Geertsma-Kleinekoort, Wendy MC; Abbas, Saman; Horsman, Sebastiaan; van der Spek, Peter J; Löwenberg, Bob; Valk, Peter JM

    Background: Accurate analyses of comprehensive genome-wide SNP genotyping and gene expression data sets is challenging for many researchers. In fact, obtaining an integrated view of both large scale SNP genotyping and gene expression is currently complicated since only a limited number of appropriate software tools are available. Results: We present SNPExpress, a software tool to accurately analyze Affymetrix and Illumina SNP genotype calls, copy numbers, polymorphic copy number variations (CNVs) and Affymetrix gene expression in a combinatorial and efficient way. In addition, SNPExpress allows concurrent interpretation of these items with Hidden-Markov Model (HMM) inferred Loss-of-Heterozygosity (LOH)- and copy number regions. Conclusion: The combined analyses with the easily accessible software tool SNPExpress will not only facilitate the recognition of recurrent genetic lesions, but also the identification of critical pathogenic genes.

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    SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

    (Springer Nature, 2009) Bass, Adam; Watanabe, Hideo; Mermel, Craig; Yu, Soyoung; Perner, Sven; Verhaak, Roel; Kim, So Jeong; Wardwell, Leslie; Tamayo, Pablo; Gat-Viks, Irit; Ramos, Alex H; Woo, Michele S; Weir, Barbara Ann; Getz, Gad; Beroukhim, Rameen; O, Michael; Dutt, Amit; Rozenblatt-Rosen, Orit; Dziunycz, Piotr; Komisarof, Justin; Chirieac, Lucian; LaFargue, Christopher J; Scheble, Veit; Wilbertz, Theresia; Ma, Changqing; Rao, Shilpa; Nakagawa, Hiroshi; Stairs, Douglas B; Lin, Lin; Giordano, Thomas J; Wagner, Patrick; Minna, John D; Gazdar, Adi F; Zhu, Chang Qi; Brose, Marcia S; Cecconello, Ivan; Jr, Ulysses Ribeiro; Marie, Suely K; Dahl, Olav; Shivdasani, Ramesh; Tsao, Ming-Sound; Rubin, Mark A; Wong, Kwok-Kin; Regev, Aviv; Hahn, William; Beer, David G; Rustgi, Anil K; Meyerson, Matthew

    Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC.