Genomic and transcriptomic analysis of a library of small cell lung cancer patient-derived xenografts.

Autor: Caeser R; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Egger JV; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Chavan S; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Socci ND; Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Jones CB; Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Kombak FE; Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Asher M; Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Roehrl MH; Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Shah NS; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Allaj V; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Manoj P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Tischfield SE; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kulick A; Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY10065, USA., Meneses M; Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY10065, USA., Iacobuzio-Donahue CA; Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lai WV; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Bhanot U; Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Baine MK; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rekhtman N; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hollmann TJ; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., de Stanchina E; Antitumor Assessment Core Facility, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY10065, USA., Poirier JT; Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA., Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. rudinc@mskcc.org.; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. rudinc@mskcc.org., Sen T; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. sent@mskcc.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Apr 19; Vol. 13 (1), pp. 2144. Date of Electronic Publication: 2022 Apr 19.
DOI: 10.1038/s41467-022-29794-4
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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