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

Autor: Gill TR; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Samy MD; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Butler SN; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Mauro JA; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA., Sexton WJ; Genitourinary Oncology Program, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA., Blanck G; 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.
Jazyk: angličtina
Zdroj: Cancer informatics [Cancer Inform] 2016 Feb 25; Vol. 15, pp. 23-8. Date of Electronic Publication: 2016 Feb 25 (Print Publication: 2016).
DOI: 10.4137/CIN.S35784
Abstrakt: 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.
Databáze: MEDLINE