期刊
JCO PRECISION ONCOLOGY
卷 1, 期 -, 页码 -出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/PO.16.00038
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资金
- National Institutes of Health (NIH) [R01CA116337, 5U01 CA111275-09]
- Conquer Cancer Foundation
- John and Elizabeth Leonard Family Foundation
- NIH/National Center for Advancing Translational Sciences [KL2TR000458]
- Damon Runyon-Gordon Family Clinical Investigator Award [CI-67-13]
- Department of Defense Prostate Cancer Research Program [PC121341]
- Starr Cancer Consortium
- Nuovo Soldati Foundation
- Associazione Italiana per la Ricerca sul Cancro [IG 13562]
- European Research Council
- Translational Research Program at Weill Cornell Medicine Pathology and Laboratory Medicine
- NATIONAL CANCER INSTITUTE [R01CA116337, U01CA111275] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [KL2TR002385, KL2TR000458, UL1TR002384] Funding Source: NIH RePORTER
Purpose Patients with cancer who graciously consent for autopsy represent an invaluable resource for the study of cancer biology. To advance the study of tumor evolution, metastases, and resistance to treatment, we developed a next-generation rapid autopsy program integrated within a broader precision medicine clinical trial that interrogates pre- and postmortem tissue samples for patients of all ages and cancer types. Materials and Methods One hundred twenty-three (22%) of 554 patients who consented to the clinical trial also consented for rapid autopsy. This report comprises the first 15 autopsies, including patients with metastatic carcinoma (n = 10), melanoma (n = 1), and glioma (n = 4). Whole-exome sequencing (WES) was performed on frozen autopsy tumor samples from multiple anatomic sites and on non-neoplastic tissue. RNA sequencing (RNA-Seq) was performed on a subset of frozen samples. Tissue was also used for the development of preclinical models, including tumor organoids and patient-derived xenografts. Results Three hundred forty-six frozen samples were procured in total. WES was performed on 113 samples and RNA-Seq on 72 samples. Successful cell strain, tumor organoid, and/or patient-derived xenograft development was achieved in four samples, including an inoperable pediatric glioma. WES data were used to assess clonal evolution and molecular heterogeneity of tumors in individual patients. Mutational profiles of primary tumors and metastases yielded candidate mediators of metastatic spread and organotropism including CUL9 and PIGM in metastatic ependymoma and ANKRD52 in metastatic melanomato the lung. RNA-Seqdata identified novel gene fusion candidates. Conclusion A next-generation sequencing-based autopsy program in conjunction with a pre-mortem precision medicine pipeline for diverse tumors affords a valuable window into clonal evolution, metastasis, and alterations underlying treatment. Moreover, such an autopsy program yields robust preclinical models of disease. (C) 2017 by American Society of Clinical Oncology
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