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s 475 Array-CGH analysis of solid tumors with apparent normal karyotypes Gokce Toruner , Zhen-Ya Tang , Deanna Streck , Lisa Osborne , Rohini Kurvathi a a Institute of Genomic Medicine, UMDNJ-NJ Medical School, Newark, NJ, USA Some solid tumors with apparent normal karyotypes are not normal. These results are false negatives and detected normal result is due to overtake of the culture by normal cells. Discard fresh tissues from 10 cases of solid tumors with apparent normal karyotype (liposarcoma, renal cell carcinoma, lymphoma, breast cancer) were analyzed by array-CGH using Agilent 44K arrays. Four cases (40%) had abnormalities detected with array CGH, which was not previously detected after conventional tissue culture and cytogenetic analysis chromosome analysis. The pilot experiments indicate that incorporation of array-CGH in routine cancer cytogenetics may be beneficial in decreasing false negative results due to cell culture issues. Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development Ian M. Wilson , William W. Lockwood , Bradley P. Coe , Raj Chari , Larissa A. Pikor , Kelsie L. Thu , John Yee , John English , Nevin Murray , Ming-Sound Tsao , John D. Minna , Adi F. Gazdar , Calum E. MacAulay , Stephen Lam , Wan L. Lam b Cancer Genetics Laboratory, Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada; Cancer Biology and Genetics Section, Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Department of Surgery, Vancouver General Hospital, West, Vancouver, BC, Canada; Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Pathology, Division of Applied Molecular Oncology, University Health Network e Princess Margaret Hospital and Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA Traditionally non-small cell lung cancer (NSCLC) has been regarded as a single disease in terms of both diagnosis and of therapy; however, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and newly developed chemotherapies. Therefore, identifying the molecular differences between these tumor types will impact diagnostic and therapeutic decisions. Here, we performed a large-scale multidimensional microarray analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC), integrating DNA copy number, DNA methylation and gene expression profiles to identify subtype-specific alterations. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with corresponding expression changes that are selected during tumor development in a subtypespecific manner. Analysis of >200 additional NSCLCs confirmed that these genes are responsible for driving the differential development and resulting phenotypes of AC and SqCC. Importantly, we identified key oncogenic pathways disrupted in each subtype that likely serve as the basis for differential behaviors in tumor biology and clinical outcomes. The possibility of using these differing oncogenic pathways to inform therapy design was then explored through an in silico screening of candidate therapeutic compounds. The robust and reproducible differences in both the genomic and epigenomic landscapes of AC and SqCC tumor highlights the future role of microarray technologies in the diagnosis and clinical management of lung and other solid tumors. |
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