High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes.
High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes.
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作者：
Choy E;Hornicek F;MacConaill L;Harmon D;Tariq Z;Garraway L;Duan Z
Identification of new genes that are mutated in osteosarcomas is critical to developing a better understanding of the molecular pathogenesis of this disease and discovering new targets for therapeutic development. We identified somatic non-synonymous coding mutations in oncogenes associated with human cancers and hotspot mutations from tumor suppressor genes that were either well-described in literature or seen multiple times in human cancer sequencing efforts. We then systematically characterized 961 mutations in 89 genes across 98 osteosarcoma tumor samples and cell lines. All identified mutations were replicated on an independent platform using homogeneous mass extend MALDI-TOF (Sequenom hME Genotyping). We identified 14 mutations in at least one osteosarcoma tumor sample or cell line. Some of the genetic changes identified were in tumor suppressor genes previously known to be altered in osteosarcoma: p53 (R273H, R273C, and Y163C) and RB1 (E137*). Notably, we identified multiple mutations in PIK3CA (H1047R, E545K, and H701P) which have never previously been observed in osteosarcoma. Additionally, we observed mutations in KRAS (G12S), CUBN (I3189V, seen in two separate tumor samples), CDH1 (A617T, seen in two separate tumor samples), CTNNB1 (N287S), and FSCB (S775L). We performed the largest mutational profiling of osteosarcoma to date and identified for the first time several mutations involving the PI3 kinase pathway – adding osteosarcoma on to the growing list of malignancies with PI3 kinase mutations. Additionally, we initiated a mutational map detailing DNA sequence changes across a variety of osteosarcoma subtypes and offered new candidates for therapeutic targeting.
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DOI：
10.1056/nejmoa1007056
发表时间：
2010-10-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Butrynski JE;D'Adamo DR;Hornick JL;Dal Cin P;Antonescu CR;Jhanwar SC;Ladanyi M;Capelletti M;Rodig SJ;Ramaiya N;Kwak EL;Clark JW;Wilner KD;Christensen JG;Jänne PA;Maki RG;Demetri GD;Shapiro GI
通讯作者：
Shapiro GI
影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
3.2
作者：
Chi, SN;Conklin, LS;Gorlick, R
通讯作者：
Gorlick, R
影响因子：
158.5
作者：
Joensuu, H;Roberts, PJ;Demetri, GD
通讯作者：
Demetri, GD
影响因子：
45.3
作者：
Feugeas, O;Guriec, N;Oberling, F
通讯作者：
Oberling, F