{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:47:03Z","timestamp":1790880423231,"version":"4.1.0"},"reference-count":33,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is believed to represent a clonal expansion of a transformed skin-resident memory T cell. T-cell receptor (TCR) clonality (ie, identical sequences of rearranged TCR\u03b1, TCR\u03b2, and TCR\u03b3), the key premise of this hypothesis, has been difficult to document conclusively because malignant cells are not readily distinguishable from the tumor-infiltrating reactive lymphocytes that contribute to the TCR clonotypic repertoire of MF. Here, we have successfully adopted targeted whole-exome sequencing (WES) to identify the repertoire of rearranged TCR genes in tumor-enriched samples from patients with MF. Although some of the investigated MF biopsies had the expected frequency of monoclonal rearrangements of TCR\u03b3 corresponding to that of tumor cells, the majority of the samples presented multiple TCR\u03b3, TCR\u03b1, and TCR\u03b2 clonotypes by WES. Our findings are compatible with the model in which the initial malignant transformation in MF does not occur in mature memory T cells but rather at the level of T-lymphocyte progenitors before TCR\u03b2 or TCR\u03b1 rearrangements. We have also shown that WES can be combined with whole-transcriptome sequencing in the same sample, which enables comprehensive characterization of the TCR repertoire in relation to tumor content. WES\/whole-transcriptome sequencing might be applicable to other types of T-cell lymphomas to determine clonal dominance and clonotypic heterogeneity in these malignancies.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018027482","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T16:56:45Z","timestamp":1554829005000},"page":"1175-1184","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":58,"title":["Clonotypic heterogeneity in cutaneous T-cell lymphoma (mycosis fungoides) revealed by comprehensive whole-exome sequencing"],"prefix":"10.1182","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7370-2378","authenticated-orcid":false,"given":"Aishwarya","family":"Iyer","sequence":"first","affiliation":[{"name":"Division of Dermatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-8524","authenticated-orcid":false,"given":"Dylan","family":"Hennessey","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"O\u2019Keefe","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB, Canada;"},{"name":"Genesis, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-8680","authenticated-orcid":false,"given":"Thomas","family":"Salopek","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gane Ka-Shu","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB, Canada;"},{"name":"Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2310-8300","authenticated-orcid":false,"given":"Robert","family":"Gniadecki","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, and"},{"name":"Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"issue":"6","key":"2020021108274036100_B1","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1182\/blood-2007-03-055749","article-title":"Revisions to the staging and classification of mycosis fungoides and S\u00e9zary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC) [published correction appears in Blood. 2008;111(9):4830]","volume":"110","author":"Olsen","year":"2007","journal-title":"Blood"},{"issue":"2","key":"2020021108274036100_B2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1182\/blood-2006-10-054601","article-title":"TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC)","volume":"110","author":"Kim","year":"2007","journal-title":"Blood"},{"issue":"10","key":"2020021108274036100_B3","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.1182\/blood-2004-09-3502","article-title":"WHO-EORTC classification for cutaneous lymphomas","volume":"105","author":"Willemze","year":"2005","journal-title":"Blood"},{"issue":"32","key":"2020021108274036100_B4","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1200\/JCO.2015.61.7142","article-title":"Cutaneous Lymphoma International Consortium Study of outcome in advanced stages of mycosis fungoides and S\u00e9zary syndrome: effect of specific prognostic markers on survival and development of a prognostic model","volume":"33","author":"Scarisbrick","year":"2015","journal-title":"J Clin Oncol"},{"issue":"4","key":"2020021108274036100_B5","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1172\/JCI24826","article-title":"Immunopathogenesis and therapy of cutaneous T cell lymphoma","volume":"115","author":"Kim","year":"2005","journal-title":"J Clin Invest"},{"issue":"6181","key":"2020021108274036100_B6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/334395a0","article-title":"T-cell antigen receptor genes and T-cell recognition [published correction appears in Nature. 1988;335(6192):744]","volume":"334","author":"Davis","year":"1988","journal-title":"Nature"},{"issue":"11","key":"2020021108274036100_B7","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/S0198-8859(99)00099-3","article-title":"Non-productive human TCR beta chain genes represent V-D-J diversity before selection upon function: insight into biased usage of TCRBD and TCRBJ genes and diversity of CDR3 region length","volume":"60","author":"Manfras","year":"1999","journal-title":"Hum Immunol"},{"issue":"1","key":"2020021108274036100_B8","doi-asserted-by":"crossref","first-page":"11881","DOI":"10.1038\/ncomms11881","article-title":"Robust estimates of overall immune-repertoire diversity from high-throughput measurements on samples","volume":"7","author":"Kaplinsky","year":"2016","journal-title":"Nat Commun"},{"issue":"440","key":"2020021108274036100_B9","doi-asserted-by":"crossref","first-page":"eaar5894","DOI":"10.1126\/scitranslmed.aar5894","article-title":"High-throughput sequencing of the T cell receptor \u03b2 gene identifies aggressive early-stage mycosis fungoides","volume":"10","author":"de Masson","year":"2018","journal-title":"Sci Transl Med"},{"issue":"2","key":"2020021108274036100_B10","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1182\/blood.V96.2.640","article-title":"High detection rate of T-cell receptor beta chain rearrangements in T-cell lymphoproliferations by family specific polymerase chain reaction in combination with the GeneScan technique and DNA sequencing","volume":"96","author":"Assaf","year":"2000","journal-title":"Blood"},{"issue":"3","key":"2020021108274036100_B11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/gene.2016.9","article-title":"Current status and recent advances of next generation sequencing techniques in immunological repertoire","volume":"17","author":"Hou","year":"2016","journal-title":"Genes Immun"},{"issue":"308","key":"2020021108274036100_B12","doi-asserted-by":"crossref","first-page":"308ra158","DOI":"10.1126\/scitranslmed.aaa9122","article-title":"TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL","volume":"7","author":"Kirsch","year":"2015","journal-title":"Sci Transl Med"},{"issue":"2","key":"2020021108274036100_B13","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jaad.2015.04.030","article-title":"T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides","volume":"73","author":"Sufficool","year":"2015","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"2020021108274036100_B14","doi-asserted-by":"crossref","first-page":"30064","DOI":"10.1038\/srep30064","article-title":"Immune DNA signature of T-cell infiltration in breast tumor exomes","volume":"6","author":"Levy","year":"2016","journal-title":"Sci Rep"},{"issue":"11","key":"2020021108274036100_B15","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1101\/gr.180281.114","article-title":"TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data","volume":"24","author":"Ha","year":"2014","journal-title":"Genome Res"},{"issue":"5","key":"2020021108274036100_B16","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nmeth.3364","article-title":"MiXCR: software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat Methods"},{"issue":"9","key":"2020021108274036100_B17","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res"},{"issue":"1","key":"2020021108274036100_B18","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12859-015-0613-1","article-title":"tcR: an R package for T cell receptor repertoire advanced data analysis","volume":"16","author":"Nazarov","year":"2015","journal-title":"BMC Bioinformatics"},{"issue":"11","key":"2020021108274036100_B19","doi-asserted-by":"crossref","first-page":"e1004503","DOI":"10.1371\/journal.pcbi.1004503","article-title":"VDJtools: unifying post-analysis of T cell receptor repertoires","volume":"11","author":"Shugay","year":"2015","journal-title":"PLOS Comput Biol"},{"issue":"5","key":"2020021108274036100_B20","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat Genet"},{"issue":"5","key":"2020021108274036100_B21","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1084\/jem.20021945","article-title":"T cell receptor gene rearrangement lineage analysis reveals clues for the origin of highly restricted antigen-specific repertoires","volume":"197","author":"Hamrouni","year":"2003","journal-title":"J. Exp. Med"},{"issue":"11","key":"2020021108274036100_B22","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1038\/nm.3359","article-title":"High-throughput identification of antigen-specific TCRs by TCR gene capture","volume":"19","author":"Linnemann","year":"2013","journal-title":"Nat Med"},{"issue":"1","key":"2020021108274036100_B23","doi-asserted-by":"crossref","first-page":"8081","DOI":"10.1038\/ncomms9081","article-title":"High-resolution analysis of the human T-cell receptor repertoire","volume":"6","author":"Ruggiero","year":"2015","journal-title":"Nat Commun"},{"issue":"1","key":"2020021108274036100_B24","doi-asserted-by":"crossref","first-page":"11301","DOI":"10.1038\/s41598-017-11310-0","article-title":"Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data","volume":"7","author":"Gong","year":"2017","journal-title":"Sci Rep"},{"issue":"5","key":"2020021108274036100_B25","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/j.1365-2133.2004.05970.x","article-title":"Polyclonal expansion of T cells with the TCR V beta type of the tumour cell in lesions of cutaneous T-cell lymphoma: evidence for possible superantigen involvement","volume":"150","author":"Linnemann","year":"2004","journal-title":"Br J Dermatol"},{"issue":"11","key":"2020021108274036100_B26","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1182\/blood.V91.11.4331","article-title":"Isolation of tumor-specific cytotoxic CD4+ and CD4+CD8dim+ T-cell clones infiltrating a cutaneous T-cell lymphoma","volume":"91","author":"Bagot","year":"1998","journal-title":"Blood"},{"issue":"5","key":"2020021108274036100_B27","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1046\/j.1365-2230.1997.2610674.x","article-title":"Lack of expression of the recombination activating genes RAG-1 and RAG-2 in cutaneous T-cell lymphoma: pathogenic implications","volume":"22","author":"D\u00f6bbeling","year":"1997","journal-title":"Clin Exp Dermatol"},{"issue":"9","key":"2020021108274036100_B28","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/ng.3356","article-title":"Genomic landscape of cutaneous T cell lymphoma","volume":"47","author":"Choi","year":"2015","journal-title":"Nat Genet"},{"key":"2020021108274036100_B29","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/978-3-642-59410-6_32","article-title":"From inflammation to neoplasia: new concepts in the pathogenesis of cutaneous lymphomas","volume":"160","author":"Burg","year":"2002","journal-title":"Recent Results Cancer Res"},{"issue":"1","key":"2020021108274036100_B30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1182\/blood.V89.1.32","article-title":"Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion","volume":"89","author":"Jackow","year":"1997","journal-title":"Blood"},{"issue":"1","key":"2020021108274036100_B31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1084\/jem.177.1.175","article-title":"Two adjacent residues in staphylococcal enterotoxins A and E determine T cell receptor V beta specificity","volume":"177","author":"Hudson","year":"1993","journal-title":"J Exp Med"},{"issue":"1","key":"2020021108274036100_B32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13073-015-0238-z","article-title":"Annotation of pseudogenic gene segments by massively parallel sequencing of rearranged lymphocyte receptor loci","volume":"7","author":"Dean","year":"2015","journal-title":"Genome Med"},{"issue":"12","key":"2020021108274036100_B33","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1111\/all.13223","article-title":"Nonlesional atopic dermatitis skin shares similar T-cell clones with lesional tissues","volume":"72","author":"Brunner","year":"2017","journal-title":"Allergy"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/3\/7\/1175\/1631477\/advances027482.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/3\/7\/1175\/1631477\/advances027482.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T08:46:20Z","timestamp":1581410780000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/3\/7\/1175\/247276\/Clonotypic-heterogeneity-in-cutaneous-Tcell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,9]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,4,9]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2018027482","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/405415","asserted-by":"object"}]},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,9]]}}}