TY - JOUR
T1 - Genomic and transcriptomic analysis of a library of small cell lung cancer patient-derived xenografts
AU - Caeser, Rebecca
AU - Egger, Jacklynn V.
AU - Chavan, Shweta
AU - Socci, Nicholas D.
AU - Jones, Caitlin Byrne
AU - Kombak, Faruk Erdem
AU - Asher, Marina
AU - Roehrl, Michael H.
AU - Shah, Nisargbhai S.
AU - Allaj, Viola
AU - Manoj, Parvathy
AU - Tischfield, Sam E.
AU - Kulick, Amanda
AU - Meneses, Maximiliano
AU - Iacobuzio-Donahue, Christine A.
AU - Lai, W. Victoria
AU - Bhanot, Umeshkumar
AU - Baine, Marina K.
AU - Rekhtman, Natasha
AU - Hollmann, Travis J.
AU - de Stanchina, Elisa
AU - Poirier, John T.
AU - Rudin, Charles M.
AU - Sen, Triparna
N1 - Funding Information:
Supported by NCI 1 R35CA263816-01, R01 CA197936, and U24 CA213274 (C.M.R.), the SU2C/VAI Epigenetics Dream Team (C.M.R.), NCI 1R01CA258784 (T.S.), the Druckenmiller Center for Lung Cancer Research (C.M.R. and T.S.), Parker Institute for Cancer Immunotherapy grant (T.S.); International Association for the Study of Lung Cancer grant (T.S.), LC190161 Congressionally Directed Medical Research Programs (DOD-IITRA) (T.S.). We acknowledge the use of the Integrated Genomics Operation Core (special thanks to Cassidy C Cobbs), funded by the NCI Cancer Center Support Grant (CCSG, P30 CA08748), Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (special thanks to Ritika Kundra and Yichao Sun) and the National Cancer Institute Cancer Center Core Grant No. P30-CA008748.The PPBC Biobank and Precision Pathology Center are supported by the NCI Cancer Center Support Grant P30-CA008748. We gratefully acknowledge the members of the Molecular Diagnostics Service in the Department of Pathology, in particular Rose Brannon. We wish to acknowledge assistance from the Bioinformatics Core which is funded in part through the NIH/NCI Cancer Center Support Grant P30-CA008748. We thank all members of the MSKCC Antitumor Assessment Core Facility (core grant: P30-CA008748 S5). We thank all members of the Rudin laboratory for their collaborative efforts.
Funding Information:
Supported by NCI 1 R35CA263816-01, R01 CA197936, and U24 CA213274 (C.M.R.), the SU2C/VAI Epigenetics Dream Team (C.M.R.), NCI 1R01CA258784 (T.S.), the Druckenmiller Center for Lung Cancer Research (C.M.R. and T.S.), Parker Institute for Cancer Immunotherapy grant (T.S.); International Association for the Study of Lung Cancer grant (T.S.), LC190161 Congressionally Directed Medical Research Programs (DOD-IITRA) (T.S.). We acknowledge the use of the Integrated Genomics Operation Core (special thanks to Cassidy C Cobbs), funded by the NCI Cancer Center Support Grant (CCSG, P30 CA08748), Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology (special thanks to Ritika Kundra and Yichao Sun) and the National Cancer Institute Cancer Center Core Grant No. P30-CA008748.The PPBC Biobank and Precision Pathology Center are supported by the NCI Cancer Center Support Grant P30-CA008748. We gratefully acknowledge the members of the Molecular Diagnostics Service in the Department of Pathology, in particular Rose Brannon. We wish to acknowledge assistance from the Bioinformatics Core which is funded in part through the NIH/NCI Cancer Center Support Grant P30-CA008748. We thank all members of the MSKCC Antitumor Assessment Core Facility (core grant: P30-CA008748 S5). We thank all members of the Rudin laboratory for their collaborative efforts.
Funding Information:
C.M.R. has consulted regarding oncology drug development with Amgen, Daiichi Sankyo, Genentech/Roche, Ipsen, Jazz, Merck, Pfizer, Syros, and Vavotek. C.M.R. serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. T.S. has research funding from Jazz Pharmaceuticals. The remaining authors declare no competing interests.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Access to clinically relevant small cell lung cancer (SCLC) tissue is limited because surgical resection is rare in metastatic SCLC. Patient-derived xenografts (PDX) and circulating tumor cell-derived xenografts (CDX) have emerged as valuable tools to characterize SCLC. Here, we present a resource of 46 extensively annotated PDX/CDX models derived from 33 patients with SCLC. We perform multi-omic analyses, using targeted tumor next-generation sequencing, RNA-sequencing, and immunohistochemistry to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these SCLC models. SCLC subtypes characterized by transcriptional regulators, ASCL1, NEUROD1 and POU2F3 are confirmed in this cohort. A subset of SCLC clinical specimens, including matched PDX/CDX and clinical specimen pairs, confirm that the primary features and genomic and proteomic landscapes of the tumors of origin are preserved in the derivative PDX models. This resource provides a powerful system to study SCLC biology.
AB - Access to clinically relevant small cell lung cancer (SCLC) tissue is limited because surgical resection is rare in metastatic SCLC. Patient-derived xenografts (PDX) and circulating tumor cell-derived xenografts (CDX) have emerged as valuable tools to characterize SCLC. Here, we present a resource of 46 extensively annotated PDX/CDX models derived from 33 patients with SCLC. We perform multi-omic analyses, using targeted tumor next-generation sequencing, RNA-sequencing, and immunohistochemistry to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these SCLC models. SCLC subtypes characterized by transcriptional regulators, ASCL1, NEUROD1 and POU2F3 are confirmed in this cohort. A subset of SCLC clinical specimens, including matched PDX/CDX and clinical specimen pairs, confirm that the primary features and genomic and proteomic landscapes of the tumors of origin are preserved in the derivative PDX models. This resource provides a powerful system to study SCLC biology.
UR - http://www.scopus.com/inward/record.url?scp=85128369002&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-29794-4
DO - 10.1038/s41467-022-29794-4
M3 - Article
C2 - 35440124
AN - SCOPUS:85128369002
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2144
ER -