title: TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL.
abstract: Early diagnosis of cutaneous T cell lymphoma (CTCL) is difficult and takes on average 6 years after presentation, in part because the clinical appearance and histopathology of CTCL can resemble that of benign inflammatory skin diseases. Detection of a malignant T cell clone is critical in making the diagnosis of CTCL, but the T cell receptor γ (TCRγ) polymerase chain reaction (PCR) analysis in current clinical use detects clones in only a subset of patients. High-throughput TCR sequencing (HTS) detected T cell clones in 46 of 46 CTCL patients, was more sensitive and specific than TCRγ PCR, and successfully discriminated CTCL from benign inflammatory diseases. HTS also accurately assessed responses to therapy and facilitated diagnosis of disease recurrence. In patients with new skin lesions and no involvement of blood by flow cytometry, HTS demonstrated hematogenous spread of small numbers of malignant T cells. Analysis of CTCL TCRγ genes demonstrated that CTCL is a malignancy derived from mature T cells. There was a maximal T cell density in skin in benign inflammatory diseases that was exceeded in CTCL, suggesting that a niche of finite size may exist for benign T cells in skin. Last, immunostaining demonstrated that the malignant T cell clones in mycosis fungoides and leukemic CTCL localized to different anatomic compartments in the skin. In summary, HTS accurately diagnosed CTCL in all stages, discriminated CTCL from benign inflammatory skin diseases, and provided insights into the cell of origin and location of malignant CTCL cells in skin.
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.
authors.forename: Ilan R
authors.initials: IR
authors.lastname: Kirsch
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rei
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Malley
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Williamson
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Laura-Louise
authors.initials: LL
authors.lastname: Scott
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Elco
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Teague
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Gehad
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Lowry
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: LeBoeuf
authors.affiliation: Department of Dermatology, Rockefeller University, New York, NY, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Adaptive Biotechnologies, Seattle, WA, USA.
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
mesh_terms: D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta