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Tumor aneuploidy predicts survival following immunotherapy across multiple cancers

An Author Correction to this article was published on 03 January 2023

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Tumor mutational burden (TMB) has emerged as a promising biomarker of immunotherapy response across multiple cancer types; however, clinical outcomes among patients with low TMB tumors are heterogeneous. Herein, we demonstrate that tumor aneuploidy provides independent prognostic value among patients with lower TMB (<80th percentile) tumors treated with immunotherapy. A higher aneuploidy score is associated with poor prognosis following immunotherapy among tumors with low TMB, but not those with high TMB. Importantly, aneuploidy scores can be calculated from existing clinical targeted sequencing infrastructure, facilitating deployment of aneuploidy scores as a clinical biomarker.

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Fig. 1: Aneuploidy and TMB are synergistic predictors of survival following immunotherapy.
Fig. 2: Defining a clinically applicable threshold of high aneuploidy.

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Data availability

All data are available from the cBioPortal study found at and the GENIE v.7.1 release:!Synapse:syn7222066/wiki/405659. Aneuploidy scores and FGA values for each sample are provided in the GitHub repository referenced below. Source data are provided with this paper.

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All code necessary to replicate these analyses are provided in the following GitHub repository:

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This work was supported by the Ludwig Cancer Research Foundation (S.P.P. and R.R.W.), a Career Development Award from the LUNGevity Foundation (S.P.P.), an Ullman Scholarship in Translational Cancer Immunology from the University of Chicago Comprehensive Cancer Center (UCCCC) (S.P.P.), a Cancer Spotlight Grant (S.P.P.) from the UCCCC, a Fight Against Cancer Grant from the United-4 A Cure Foundation (S.P.P.) and a National Institutes of Health NCI-SOAR Grant 1R25CA240134-01 (L.F.S.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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All authors contributed to the conceptualization, investigation, visualization, writing and editing of this work.

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Correspondence to Sean P. Pitroda.

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L.F.S. declares no competing interests. R.R.W. reports having stock and other ownership interests with Boost Therapeutics, ImmVira LLC, Reflexion Pharmaceuticals, Coordination Pharmaceuticals Inc., Magi Therapeutics and Oncosenescence; serving in a consulting or advisory role for Aettis Inc., AstraZeneca, Coordination Pharmaceuticals, Genus, Merck Serono S.A., NanoProteagen, NKMax America Inc., Shuttle Pharmaceuticals and Highlight Therapeutics, S.L.; having research grants with Varian and Regeneron; and receiving compensation including travel, accommodations or expense reimbursement from AstraZeneca, Boehringer Ingelheim Ltd. and Merck Serono S.A. S.P.P. has patents outside of the submitted work.

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Nature Genetics thanks Douglas Johnson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Spurr, L.F., Weichselbaum, R.R. & Pitroda, S.P. Tumor aneuploidy predicts survival following immunotherapy across multiple cancers. Nat Genet 54, 1782–1785 (2022).

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