Personalized oncogenomics in the management of gastrointestinal carcinomas— early experiences from a pilot study

Current oncology

D.F. Schaeffer¹  H.J. Lim²  J. Laskin²  D.J. Renouf²  K. Kasaian³  S.J.M. Jones³  Y. Li³  Y. Shen³  E. Pleasance⁴  M. Marra⁵  H. Li-Chang⁵  S. Yip⁶  D.G. Huntsman⁶  B. Tessier-Cloutier⁶  B.S. Sheffield⁶ 

[1] University of British Columbia;BC Cancer Agency;Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency;Michael Smith Genome Sciences Centre;Royal Victoria Regional Health Centre;University of British Columbia

关键词: Oncogenomics;    genomics;    cholangiocarcinoma;    colonic adenocarcinoma;    appendiceal adenocarcinoma;    targeted therapy;    personalized medicine;    bevacizumab;   

DOI  :  10.3747/co.23.3165

学科分类：肿瘤学

来源: Multimed, Inc.

【 摘 要 】

BackgroundGastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. MethodsWe report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. ResultsIn the first case, genomic profiling revealed anIDH1somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, aBRAFV600E mutation and wild-typeKRASprofile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. SummaryWe show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information. 

【 授权许可】

Unknown