TY - JOUR A1 - Belinsky, Martin G. A1 - Rink, Lori A1 - Cai, Kathy Q. A1 - Capuzzi, Stephen J. A1 - Hoang, Yen A1 - Chien, Jeremy A1 - Godwin, Andrew K. A1 - von Mehren, Margaret T1 - 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 JF - BMC Cancer N2 - 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. KW - gastrointestinal stromal tumor (GIST) KW - wild type KW - KIT KW - PDGFRA KW - succinate dehydrogenase (SDH) KW - NF1 KW - MAX Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6292 SN - 1471-2407 VL - 15 IS - 887 ER - TY - JOUR A1 - Munchel, Sarah A1 - Hoang, Yen A1 - Zhao, Yue A1 - Cottrell, Joseph A1 - Klotzle, Brandy A1 - Godwin, Andrew K. A1 - Koestler, Devin A1 - Beyerlein, Peter A1 - Fan, Jian-Bing A1 - Bibikova, Marina A1 - Chien, Jeremy T1 - Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics JF - Oncotarget N2 - 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. KW - cancer genomics KW - FFPE DNA KW - whole exome sequencing KW - whole genome sequencing KW - copy number alteration Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6307 SN - 1949-2553 VL - 6 IS - 28 SP - 25943 EP - 25961 ER -