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

Author

Listed:
  • Rebecca Caeser

    (Memorial Sloan Kettering Cancer Center)

  • Jacklynn V. Egger

    (Memorial Sloan Kettering Cancer Center)

  • Shweta Chavan

    (Memorial Sloan Kettering Cancer Center)

  • Nicholas D. Socci

    (Bioinformatics Core, Memorial Sloan Kettering Cancer Center)

  • Caitlin Byrne Jones

    (Bioinformatics Core, Memorial Sloan Kettering Cancer Center)

  • Faruk Erdem Kombak

    (Memorial Sloan Kettering Cancer Center)

  • Marina Asher

    (Memorial Sloan Kettering Cancer Center)

  • Michael H. Roehrl

    (Memorial Sloan Kettering Cancer Center)

  • Nisargbhai S. Shah

    (Memorial Sloan Kettering Cancer Center)

  • Viola Allaj

    (Memorial Sloan Kettering Cancer Center)

  • Parvathy Manoj

    (Memorial Sloan Kettering Cancer Center)

  • Sam E. Tischfield

    (Memorial Sloan Kettering Cancer Center)

  • Amanda Kulick

    (Memorial Sloan Kettering Cancer Center)

  • Maximiliano Meneses

    (Memorial Sloan Kettering Cancer Center)

  • Christine A. Iacobuzio-Donahue

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • W. Victoria Lai

    (Memorial Sloan Kettering Cancer Center)

  • Umeshkumar Bhanot

    (Memorial Sloan Kettering Cancer Center)

  • Marina K. Baine

    (Memorial Sloan Kettering Cancer Center)

  • Natasha Rekhtman

    (Memorial Sloan Kettering Cancer Center)

  • Travis J. Hollmann

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Elisa Stanchina

    (Memorial Sloan Kettering Cancer Center)

  • John T. Poirier

    (New York University Langone Health)

  • Charles M. Rudin

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Triparna Sen

    (Memorial Sloan Kettering Cancer Center)

Abstract

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.

Suggested Citation

  • Rebecca Caeser & Jacklynn V. Egger & Shweta Chavan & Nicholas D. Socci & Caitlin Byrne Jones & Faruk Erdem Kombak & Marina Asher & Michael H. Roehrl & Nisargbhai S. Shah & Viola Allaj & Parvathy Manoj, 2022. "Genomic and transcriptomic analysis of a library of small cell lung cancer patient-derived xenografts," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29794-4
    DOI: 10.1038/s41467-022-29794-4
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