TY - JOUR
T1 - Next-generation rapid autopsies enable tumor evolution tracking andgeneration of preclinical models
AU - Pisapia, David J.
AU - Salvatore, Steven
AU - Pauli, Chantal
AU - Hissong, Erika
AU - Eng, Ken
AU - Prandi, Davide
AU - Sailer, Verena Wilbeth
AU - Robinson, Brian D.
AU - Park, Kyung
AU - Cyrta, Joanna
AU - Tagawa, Scott T.
AU - Kossai, Myriam
AU - Fontugne, Jacqueline
AU - Kim, Robert
AU - Sigaras, Alexandros
AU - Rao, Rema
AU - Pancirer, Danielle
AU - Faltas, Bishoy
AU - Bareja, Rohan
AU - Molina, Ana M.
AU - Nanus, David M.
AU - Rajappa, Prajwal
AU - Souweidane, Mark M.
AU - Greenfield, Jeffrey
AU - Emde, Anne Katrin
AU - Robine, Nicolas
AU - Elemento, Olivier
AU - Sboner, Andrea
AU - Demichelis, Francesca
AU - Beltran, Himisha
AU - Rubin, Mark A.
AU - Mosquera, Juan Miguel
N1 - Publisher Copyright:
© 2018 American Society of Clinical Oncology.
PY - 2017
Y1 - 2017
N2 - 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.WESwas performed on 113 samples and RNA-Seq on 72 samples. Successful cell strain, tumor organoid, and/or patientderived xenograft development was achieved in four samples, including an inoperable pediatric glioma.WESdata 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 ependymomaandANKRD52in metastaticmelanomato the lung.RNA-Seqdata identified novel gene fusion candidates. Conclusion A next-generation sequencing-based autopsy program in conjunction with a premortem 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.
AB - 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.WESwas performed on 113 samples and RNA-Seq on 72 samples. Successful cell strain, tumor organoid, and/or patientderived xenograft development was achieved in four samples, including an inoperable pediatric glioma.WESdata 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 ependymomaandANKRD52in metastaticmelanomato the lung.RNA-Seqdata identified novel gene fusion candidates. Conclusion A next-generation sequencing-based autopsy program in conjunction with a premortem 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.
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U2 - 10.1200/PO.16.00038
DO - 10.1200/PO.16.00038
M3 - Article
AN - SCOPUS:85045541585
SN - 2473-4284
VL - 2017
SP - 1
EP - 13
JO - JCO Precision Oncology
JF - JCO Precision Oncology
IS - 1
ER -