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Comprehensive genomic profiling using high-throughput sequencing brings a wealth of information, and its place in the clinical setting has been increasingly prominent. This review emphasizes the utility of whole-exome sequencing (WES) and transcriptome sequencing (RNAseq) in patient care and clinical research, based on published reports as well as our experience with the MOSCATO-01 (MOlecular Screening for CAncer Treatment Optimization) molecular triage trial at Gustave Roussy Cancer Center. In this trial, all contributive samples of patients with advanced solid tumors were analyzed prospectively with targeted gene sequencing (TGS) and comparative genomic hybridization. In addition, 92 consecutive metastatic patients with contributive biopsies were sequenced for WES and RNAseq and compared with TGS and comparative genomic hybridization. Whole-exome sequencing allowed the reporting of additional variants in relevant genes in 38% of patients. Mutation detection sensitivity of WES was 95% compared with TGS. Additional information derived from WES and RNAseq could influence clinical decision, including fusion transcripts, expression levels, allele-specific expression, alternate transcripts, RNA-based pathogen diagnostic, tumor mutation load, mutational signatures, expression signatures, HLA genotyping, and neoepitope prediction. The current challenge is to be able to process the large-scale data from these comprehensive genome-wide technologies in an efficient way.

Post-translational modifications of histones are important components of chromatin-level control of genome activity in eukaryotes. In order to clarify the biological function of chromatin marks, classification methods have been developed that partition genomic regions based on their chromatin composition. Spatial enrichment of histone modifications over genes is one of the many epigenomic dimensions that reflect the impact of chromatin dynamics on gene regulation. Using a clustering approach, we have classified genes according to their H3K27me3 and H3K4me3 marking in Arabidopsis leaves and find that multiple spatial profiles with specific functional properties can be distinguished in both cases. In particular, we show that different profiles specify distinct levels of gene expression. In addition, we find that genes with different H3K27me3 profiles can be distinguished by the length of their first intron and that the length of the first exon is an important parameter that shapes the distinct H3K4me3 profi...

Despite evolutionary conserved mechanisms to silence transposable element activity, there are drastic differences in the abundance of transposable elements even among closely related plant species. We conducted a de novo assembly for the 375 Mb genome of the perennial model plant, Arabis alpina. Analysing this genome revealed long-lasting and recent transposable element activity predominately driven by Gypsy long terminal repeat retrotransposons, which extended the low-recombining pericentromeres and transformed large formerly euchromatic regions into repeat-rich pericentromeric regions. This reduced capacity for long terminal repeat retrotransposon silencing and removal in A. alpina co-occurs with unexpectedly low levels of DNA methylation. Most remarkably, the striking reduction of symmetrical CG and CHG methylation suggests weakened DNA methylation maintenance in A. alpina compared with Arabidopsis thaliana. Phylogenetic analyses indicate a highly dynamic evolution of some components of methylation maintenance machinery that might be related to the unique methylation in A. alpina. Fil: Willing, Eva Maria. Max Planck Institute for Plant Breeding Research; Alemania Fil: Rawat, Vimal. Central European Institute of Technology; República Checa Fil: Mandáková, Terezie. Central European Institute of Technology; República Checa Fil: Maumus, Florian. INRA. Research Unit in Genomics; Francia Fil: James, Geo Velikkakam. Max Planck Institute for Plant Breeding Research; Alemania Fil: Nordström, Karl J. V.. Max Planck Institute for Plant Breeding Research; Alemania Fil: Becker, Claude. Max Planck Institute for Developmental Biology; Alemania Fil: Warthmann, Norman. Max Planck Institute for Developmental Biology; Alemania. The Australian National University; Australia Fil: Chica, Claudia. Centre National de la Recherche Scientifique; Francia Fil: Szarzynska, Bogna. Centre National de la Recherche Scientifique; Francia Fil: Zytnicki, Matthias. Max Planck Institute for Developmental Biology; Alemania Fil: Albani, Maria C.. Max Planck Institute for Plant Breeding Research; Alemania Fil: Kiefer, Christiane. Max Planck Institute for Plant Breeding Research; Alemania Fil: Bergonzi, Sara. Max Planck Institute for Plant Breeding Research; Alemania Fil: Castaings, Loren. Max Planck Institute for Plant Breeding Research; Alemania Fil: Mateos, Julieta Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Max Planck Institute for Plant Breeding Research; Alemania Fil: Berns, Markus C.. Max Planck Institute for Plant Breeding Research; Alemania Fil: Bujdoso, Nora. Max Planck Institute for Plant Breeding Research; Alemania Fil: Piofczyk, Thomas. Max Planck Institute for Plant Breeding Research; Alemania Fil: Roudier, François. Centre National de la Recherche Scientifique; Francia Fil: Carbonero, Pilar. Universidad Politécnica de Madrid; España Fil: Paz Ares, Javier. Consejo Superior de Investigaciones Cientificas; España Fil: Davis, Seth J.. Max Planck Institute for Plant Breeding Research; Alemania Fil: Pecinka, Ales. Max Planck Institute for Plant Breeding Research; Alemania Fil: Quesneville, Hadi. INRA. Research Unit in Genomics; Francia Fil: Colot, Vincent. Centre National de la Recherche Scientifique; Francia Fil: Lysak, Martin A.. Central European Institute of Technology; República Checa Fil: Weigel, Detlef. Max Planck Institute for Developmental Biology; Alemania Fil: Coupland, George. Max Planck Institute for Plant Breeding Research; Alemania Fil: Schneeberger, Korbinian. Max Planck Institute for Plant Breeding Research; Alemania

5573Background: Many HGOC are genomically unstable which likely explains their chemosensitivity. How GI changes with NACT, or relates to tumor immune infiltration and prognosis is poorly described....

5575 Background: Most studies of OC have analysed tumors at diagnosis, little is known about the evolution of the genomic or immune landscape of OC with NC. Profiling after NC may be informative as...