@article{BelinskyRinkCaietal.2015, author = {Belinsky, Martin G. and Rink, Lori and Cai, Kathy Q. and Capuzzi, Stephen J. and Hoang, Yen and Chien, Jeremy and Godwin, Andrew K. and von Mehren, Margaret}, title = {Somatic loss of function mutations in neurofibromin 1 and MYC associated factor X genes identified by exome-wide sequencing in a wild-type GIST case}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {887}, issn = {1471-2407}, doi = {10.1186/s12885-015-1872-y}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6292}, year = {2015}, abstract = {Approximately 10-15 \% of gastrointestinal stromal tumors (GISTs) lack gain of function mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) genes. An alternate mechanism of oncogenesis through loss of function of the succinate-dehydrogenase (SDH) enzyme complex has been identified for a subset of these "wild type" GISTs.}, language = {en} } @article{MunchelHoangZhaoetal.2015, author = {Munchel, Sarah and Hoang, Yen and Zhao, Yue and Cottrell, Joseph and Klotzle, Brandy and Godwin, Andrew K. and Koestler, Devin and Beyerlein, Peter and Fan, Jian-Bing and Bibikova, Marina and Chien, Jeremy}, title = {Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {28}, issn = {1949-2553}, doi = {10.18632/oncotarget.4671}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6307}, pages = {25943 -- 25961}, year = {2015}, abstract = {Current genomic studies are limited by the poor availability of fresh-frozen tissue samples. Although formalin-fixed diagnostic samples are in abundance, they are seldom used in current genomic studies because of the concern of formalin-fixation artifacts. Better characterization of these artifacts will allow the use of archived clinical specimens in translational and clinical research studies. To provide a systematic analysis of formalin-fixation artifacts on Illumina sequencing, we generated 26 DNA sequencing data sets from 13 pairs of matched formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples. The results indicate high rate of concordant calls between matched FF/FFPE pairs at reference and variant positions in three commonly used sequencing approaches (whole genome, whole exome, and targeted exon sequencing). Global mismatch rates and C·G > T·A substitutions were comparable between matched FF/FFPE samples, and discordant rates were low (<0.26\%) in all samples. Finally, low-pass whole genome sequencing produces similar pattern of copy number alterations between FF/FFPE pairs. The results from our studies suggest the potential use of diagnostic FFPE samples for cancer genomic studies to characterize and catalog variations in cancer genomes.}, language = {en} } @article{GrawMeierMinnetal.2015, author = {Graw, Stefan and Meier, Richard and Minn, Kay and Bloomer, Clark and Godwin, Andrew K. and Fridley, Brooke and Vlad, Anda and Beyerlein, Peter and Chien, Jeremy}, title = {Robust gene expression and mutation analyses of RNA-sequencing of formalin-fixed diagnostic tumor samples}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, issn = {2045-2322}, doi = {10.1038/srep12335}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6319}, pages = {11}, year = {2015}, abstract = {Current genomic studies are limited by the availability of fresh tissue samples. Here, we show that Illumina RNA sequencing of formalin-fixed diagnostic tumor samples produces gene expression that is strongly correlated with matched frozen tumor samples (r > 0.89). In addition, sequence variations identified from FFPE RNA show 99.67\% concordance with that from exome sequencing of matched frozen tumor samples. Because FFPE is a routine diagnostic sample preparation, the feasibility results reported here will facilitate the setup of large-scale research and clinical studies in medical genomics that are currently limited by the availability of fresh frozen samples.}, language = {en} }