American Association for Cancer Research
Browse

sorry, we can't preview this file

cd-21-1207_supplementary_table_s11_suppst11.xlsx (11.8 kB)

Supplementary Table from Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma

Download (11.8 kB)
dataset
posted on 2023-04-04, 00:04 authored by Xiaofei Song, Shiun Chang, Lucia Seminario-Vidal, Alvaro de Mingo Pulido, Leticia Tordesillas, Xingzhi Song, Rhianna A. Reed, Andrea Harkins, Shannen Whiddon, Jonathan V. Nguyen, Carlos Moran Segura, Chaomei Zhang, Sean Yoder, Zena Sayegh, Yun Zhao, Jane L. Messina, Carly M. Harro, Xiaohui Zhang, José R. Conejo-Garcia, Anders Berglund, Lubomir Sokol, Jianhua Zhang, Paulo C. Rodriguez, James J. Mulé, Andrew P. Futreal, Kenneth Y. Tsai, Pei-Ling Chen
Supplementary Table from Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma

Funding

Cancer Center Support Grant

National Cancer Institute

Find out more...

NIH

History

ARTICLE ABSTRACT

Cutaneous T-cell lymphoma (CTCL) is a rare cancer of skin-homing T cells. A subgroup of patients develops large cell transformation with rapid progression to an aggressive lymphoma. Here, we investigated the transformed CTCL (tCTCL) tumor ecosystem using integrative multiomics spanning whole-exome sequencing (WES), single-cell RNA sequencing, and immune profiling in a unique cohort of 56 patients. WES of 70 skin biopsies showed high tumor mutation burden, UV signatures that are prognostic for survival, exome-based driver events, and most recurrently mutated pathways in tCTCL. Single-cell profiling of 16 tCTCL skin biopsies identified a core oncogenic program with metabolic reprogramming toward oxidative phosphorylation (OXPHOS), cellular plasticity, upregulation of MYC and E2F activities, and downregulation of MHC I suggestive of immune escape. Pharmacologic perturbation using OXPHOS and MYC inhibitors demonstrated potent antitumor activities, whereas immune profiling provided in situ evidence of intercellular communications between malignant T cells expressing macrophage migration inhibitory factor and macrophages and B cells expressing CD74. Our study contributes a key resource to the community with the largest collection of tCTCL biopsies that are difficult to obtain. The multiomics data herein provide the first comprehensive compendium of genomic alterations in tCTCL and identify potential prognostic signatures and novel therapeutic targets for an incurable T-cell lymphoma.This article is highlighted in the In This Issue feature, p. 1171

Usage metrics

    Cancer Discovery

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC