Display options
Share it on

Cancer Inform. 2016 Feb 25;15:23-8. doi: 10.4137/CIN.S35784. eCollection 2016.

Detection of Productively Rearranged TcR-α V-J Sequences in TCGA Exome Files: Implications for Tumor Immunoscoring and Recovery of Antitumor T-cells.

Cancer informatics

Thomas R Gill, Mohammad D Samy, Shanitra N Butler, James A Mauro, Wade J Sexton, George Blanck

Affiliations

  1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
  2. Genitourinary Oncology Program, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
  3. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.; Immunology Program, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

PMID: 26966347 PMCID: PMC4768948 DOI: 10.4137/CIN.S35784

Abstract

Tumor immunoscoring is rapidly becoming a universal parameter of prognosis, and T-cells isolated from tumor masses are used for ex vivo amplification and readministration to patients to facilitate an antitumor immune response. We recently exploited the cancer genome atlas (TCGA) RNASeq data to assess T-cell receptor (TcR) expression and, in particular, discovered strong correlations between major histocompatibility class II (MHCII) and TcR-α constant region expression levels. In this article, we describe the results of searching TCGA exome files for TcR-α V-regions, followed by searching the V-region datasets for TcR-α-J regions. Both primary and metastatic breast cancer sample files contained recombined TcR-α V-J regions, ranging in read counts from 16-39, at the higher level. Among four such V-J rearrangements, three were productive rearrangements. Rearranged TcR-α V-J regions were also detected in TCGA-bladder cancer, -lung cancer, and -ovarian cancer datasets, as well as exome files representing bladder cancer, in Moffitt Cancer Center patients. These results suggest that a direct search of commonly available, conventional exome files for rearranged TcR segments could play a role in more sophisticated immunoscoring or in identifying particular T-cell clones and TcRs directed against tumor antigens.

Keywords: T-cell receptor rearrangement; TCGA; bladder cancer; breast cancer; exome; the cancer genome atlas

References

  1. Methods Mol Biol. 2012;882:569-604 - PubMed
  2. J Biol Response Mod. 1990 Aug;9(4):431-8 - PubMed
  3. Adv Exp Med Biol. 2011;714:151-72 - PubMed
  4. Cell Tissue Res. 2016 Feb;363(2):491-6 - PubMed
  5. Cancer Immunol Immunother. 2001 May;50(3):134-40 - PubMed
  6. Nat Med. 2013 Nov;19(11):1534-41 - PubMed
  7. J Immunol. 2014 Jun 15;192(12):5451-8 - PubMed
  8. Oncoimmunology. 2015 Jul 1;4(12):e1040219 - PubMed
  9. Cell Adh Migr. 2007 Jan-Mar;1(1):2-6 - PubMed
  10. Cancer Metastasis Rev. 1984;3(1):5-24 - PubMed
  11. Anticancer Res. 2015 Jan;35(1):25-9 - PubMed
  12. Cell. 2000 Oct 27;103(3):481-90 - PubMed

Publication Types