期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：43
页码：13308-13311
DOI：10.1073/pnas.1516689112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceChemotherapy has been proven in clinical studies to improve overall survival significantly. Unfortunately, there is a significant degree of heterogeneity in tumor chemosensitivity, often resulting in unnecessary treatment and needless exposure to toxic side-effects. A platform is needed that can identify preemptively which patients will or will not benefit from treatment. Tumor organoids, 3D cultures of cancer cells, present such an individualized platform. In this study we demonstrate that organoid cultures can be established from metastatic biopsy specimens with a high success rate and genetically represent the metastasis they were derived from. These data support the translation of this innovative technology to the clinic as an ex vivo screening platform for tailoring treatment. Tumor organoids are 3D cultures of cancer cells. They can be derived from the tumor of each individual patient, thereby providing an attractive ex vivo assay to tailor treatment. Using patient-derived tumor organoids for this purpose requires that organoids derived from biopsies maintain the genetic diversity of the in vivo tumor. In this study tumor biopsies were obtained from 14 patients with metastatic colorectal cancer (i) to test the feasibility of organoid culture from metastatic biopsy specimens and (ii) to compare the genetic diversity of patient-derived tumor organoids and the original tumor biopsy. Genetic analysis was performed using SOLiD sequencing for 1,977 cancer-relevant genes. Copy number profiles were generated from sequencing data using CopywriteR. Here we demonstrate that organoid cultures can be established from tumor biopsies of patients with metastatic colorectal cancer with a success rate of 71%. Genetic analysis showed that organoids reflect the metastasis from which they were derived. Ninety percent of somatic mutations were shared between organoids and biopsies from the same patient, and the DNA copy number profiles of organoids and the corresponding original tumor show a correlation of 0.89. Most importantly, none of the mutations that were found exclusively in either the tumor or organoid culture are in driver genes or genes amenable for drug targeting. These findings support further exploration of patient-derived organoids as an ex vivo platform to personalize anticancer treatment.
关键词：biopsy-derived tumor organoids ; colorectal cancer ; DNA sequencing ; copy number analysis ; personalized medicine
