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T cell clonality assessment: past, present and future

Abstract

T cell clonality testing has important clinical and research value, providing a specific and reproducible assessment of clonal diversity in T cell proliferations. Here we review the conceptual foundations of T cell clonality assays, including T cell ontogeny and T cell receptor structure and function; we also provide an introduction to T cell receptor genomics and the concept of the T cell clonotype. This is followed by a review of historical and current methods by which T cell clonality may be assayed, including current assay limitations. Some of these assay limitations have been overcome by employing next-generation sequencing (NGS)-based technologies that are becoming a mainstay of modern molecular pathology. In this vein, we provide an introduction to NGS technologies, including a review of the preanalytical, analytical and postanalytical technologies relevant to T cell clonality NGS assays.

  • lymphocytes
  • molecular pathology
  • genetics
  • oncology

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Handling editor Runjan Chetty

  • Contributors All authors have contributed to, reviewed and approved of the manuscript.

  • Funding EM was supported by a Terry Fox Foundation/Canadian Institutes of Health Research Fellowship and is currently supported by Calgary Lab Services and the University of Calgary Hematology Research Grants. TP’s work related to immune cell clonality testing is supported by grants from the Princess Margaret Cancer Foundation, Canada Foundation for Innovation, Canadian Cancer Society Research Institute, Terry Fox Research Institute, the Multiple Myeloma Research Foundation, and the Ontario Institute for Cancer Research. SK-R has received funding from Pfizer Canada and from the Princess Margaret Cancer Foundation.

  • Competing interests TP and EM are listed as inventors on a patent for profiling immune cell repertoires using hybrid capture and next-generation sequencing methods. SK-R has not competing interest to declare.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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