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T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer

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Abstract

Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer. We found that bladder cancer exomes with productive TcR-β recombinations had a significant association with No Subsequent Tumors and a positive response to drug treatments, with p < 0.004, p < 0.05, and p < 0.004, depending on the sample sets examined. We also discovered the opportunity to detect productive TcR-γ and TcR-δ recombinations in the tumor microenvironment, via the tumor specimen exome files.

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Abbreviations

BAM:

Binary alignment map

BLCA:

Bladder cancer

CAR:

Chimeric antigen receptor

IMGT:

Immuno gene tics

MHC:

Major histocompatibility complex

STAD:

Stomach adenocarcinoma

TCGA:

The cancer genome atlas

USF:

University of South Florida

WXS:

Exome

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Acknowledgements

Authors wish to acknowledge the funding of the Anna Valentine program; the assistance of the University of South Florida research computing, particularly Dr. Tony Green; and the support of the taxpayers of the State of Florida.

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Correspondence to George Blanck.

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All authors declare that they have no conflict of interest.

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Samy, M.D., Tong, W.L., Yavorski, J.M. et al. T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer. Cancer Immunol Immunother 66, 403–410 (2017). https://doi.org/10.1007/s00262-016-1943-1

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