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Recovery of T-cell receptor V(D)J recombination reads from lower grade glioma exome files correlates with reduced survival and advanced cancer grade

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Abstract

Background

The immune system plays an important role in cancer survival and disease progression, but the role of the immune system in lower grade glioma (LGG) is largely unknown

Methods

To investigate the relationship between lymphocyte infiltration into the LGG microenvironment and LGG survival, we used a genomics approach to recover productive V(D)J recombination sequences from primary tumor, whole exome sequence files available via the cancer genome atlas

Results

Increased T-cell receptor V(D)J read recovery, indicating increased T-lymphocyte infiltration into the primary tumor site, strongly correlated with decreased overall and disease-free survival; and with a more advanced cancer grade. In addition, this result was more significant than related results obtainable using RNASeq-based, T-cell biomarkers, similar to a recently reported case for pancreatic cancer, where the recovery of BCR recombination reads from WXS files clearly associated with reduced survival, despite the fact that no such association was demonstrable with B-cell based, RNASeq biomarkers

Conclusions

Overall, the results presented here support V(D)J recombination read recovery, from whole exome files, as a uniquely useful biomarker for distinct LGG survival rates.

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Abbreviations

BCR:

B-cell receptor

HUGO:

Human genome organization

KM:

Kaplan–Meier survival curve

LGG:

Lower grade glioma

TCGA:

The cancer genome atlas

TCR:

T-cell receptor

TRA, TRB:

T-cell receptor alpha and beta

WHO:

World health organization

WXS:

Whole exome sequence file

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Acknowledgements

Authors wish to acknowledge the support of USF research computing and the taxpayers of the State of Florida. BC, SZ, and AD are recipients of USF Morsani College of Medicine RISE fellowships.

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Authors and Affiliations

  1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901, Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA

    Boris I. Chobrutskiy, Saif Zaman, Wei Lue Tong, Andrea Diviney & George Blanck

  2. Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    George Blanck

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  1. Boris I. Chobrutskiy
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Contributions

BIC and WLT wrote the code that established the DNA sequencing reads as VJ recombinations. BIC also contributed extensively to analyzing the results of the mining of the exome files for the immune receptor recombination reads and to the manuscript writing. SZ contributed to the RNASeq analyses. AD conducted the Kaplan–Meier analysis. GB supervised the project, contributed to all aspects of analyses, and contributed to finalizing the manuscript.

Corresponding author

Correspondence to George Blanck.

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Chobrutskiy, B.I., Zaman, S., Tong, W.L. et al. Recovery of T-cell receptor V(D)J recombination reads from lower grade glioma exome files correlates with reduced survival and advanced cancer grade. J Neurooncol 140, 697–704 (2018). https://doi.org/10.1007/s11060-018-03001-1

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