{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:59:35Z","timestamp":1792195175087,"version":"4.4.0"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Peripheral T-Cell lymphoma (PTCL) comprises a heterogenous group of uncommon lymphomas derived from mature, post-thymic or \u201cperipheral\u201d T- and natural killer cells. The World Health Organization (WHO) emphasizes a multiparameter approach in the diagnosis and subclassification of these neoplasms, integrating clinical, morphologic, immunophenotypic, and genetic features into the final diagnosis. Clinical presentation is particularly important due to histologic, immunophenotypic and genetic variations within established subtypes, and no convenient immunophenotypic marker of monoclonality exists. In recent years, widespread use of gene expression profiling and next-generation sequencing (NGS) techniques have contributed to an improved understanding of the pathobiology in PTCLs, and these have been incorporated into the 2016 revised WHO classification of mature T- and NK-cell neoplasms which now encompasses nearly 30 distinct entities. This review discusses the genetic landscape of PTCL and its role in subclassification, prognosis, and potential targeted therapy. In addition to discussing T-Cell lymphoma subtypes with relatively well-defined or relevant genetic aberrancies, special attention is given to genetic advances in T-Cell lymphomas of T follicular helper cell (TFH) origin, highlighting genetic overlaps between angioimmunoblastic T-Cell lymphoma (AITL), follicular T-Cell lymphoma, and nodal peripheral T-Cell lymphoma with a TFH phenotype. Furthermore, genetic drivers will be discussed for ALK-negative anaplastic large cell lymphomas and their role in differentiating these from CD30+ peripheral T-Cell lymphoma, not otherwise specified (NOS) and primary cutaneous anaplastic large cell lymphoma. Lastly, a closer look is given to genetic pathways in peripheral T-Cell lymphoma, NOS, which may guide in teasing out more specific entities in a group of T-Cell lymphomas that represents the most common subcategory and is sometimes referred to as a \u201cwastebasket\u201d category.<\/jats:p>","DOI":"10.3390\/life12030410","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T12:58:36Z","timestamp":1647003516000},"page":"410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic Landscape of Peripheral T-Cell Lymphoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Vivian","family":"Hathuc","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Saint Louis University, St. Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Kreisel","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Saint Louis University, St. Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.immuni.2018.01.007","article-title":"Human T Cell Development, Localization, and Function throughout Life","volume":"48","author":"Kumar","year":"2018","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jcp.56.1.1","article-title":"Diagnostic role of tests for T cell receptor (TCR) genes","volume":"56","author":"Hodges","year":"2003","journal-title":"J. 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