High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes.

摘要: BACKGROUND: The identification of new genes that are mutated in osteosarcomas is critical to developing a better understanding the molecular pathogenesis this disease and discovering targets for therapeutic development. METHODS: The authors identified somatic nonsynonymous coding mutations oncogenes associated with human cancers hotspot from tumor suppressor were either well described literature or observed multiple times cancer sequencing efforts. Then, 961 89 systematically characterized across 98 osteosarcoma samples cell lines. All replicated on an independent platform using homogeneous mass extend matrix-assisted laser desorption/ionization time-of-flight spectrometry. RESULTS: In total, 14 at least 1 sample line. Some genetic changes previously as altered osteosarcoma: p53 (argininehistidine codon 273 [R273H], Rcysteine 723 [R273C], tyrosineC 163 [Y163C]) retinoblastoma (RB1) (glutamic acid* 137 [E137*]). Notably, phosphoinositide-3-kinase (PI3K), catalytic, alpha polypeptide (PIK3CA) (H1047R, Elysine 545 [E545K], Hproline 701 [H701P]) not osteosarcoma. In addition, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (glycineserine 12 [G12S]); cubilin (CUBN) (isolucinevaline 3189 [I3189V]; 2 separate samples); cadherin 1, type epithelial (CDH1) (alaninethreonine 617 [A617T]; catenin (cadherin-associated protein), beta 88 kDa (CTNNB1) (asparagineS 287 [N287S]); fibrous sheath CABYR binding protein (FSCB) (Sleucine 775 [S775L]) observed. CONCLUSIONS: In largest mutational profiling date, first time several involving PI3K pathway, adding growing list malignancies mutations. they initiated map detailing DNA sequence variety subtypes offered candidates targeting. Cancer 2011. © 2011 American Society.