{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:45:47Z","timestamp":1793151947599,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["FI21\/00390"],"award-info":[{"award-number":["FI21\/00390"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Primary cutaneous lymphomas comprise a heterogeneous group of extranodal non-Hodgkin lymphomas (NHL) that arise from skin resident lymphoid cells and are manifested by specific lymphomatous cutaneous lesions with no evidence of extracutaneous disease at the time of diagnosis. They may originate from mature T-lymphocytes (70% of all cases), mature B-lymphocytes (25\u201330%) or, rarely, NK cells. Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of T-cell malignancies including Mycosis Fungoides (MF) the most frequent subtype, accounting for approximately half of CTCL, and S\u00e9zary syndrome (SS), which is an erythrodermic and leukemic subtype characterized by significant blood involvement. The mutational landscape of MF and SS by NGS include recurrent genomic alterations in the TCR signaling effectors (i.e., PLCG1), the NF-\u03baB elements (i.e., CARD11), DNA damage\/repair elements (TP53 or ATM), JAK\/STAT pathway elements or epigenetic modifiers (DNMT3). Genomic copy number variations appeared to be more prevalent than somatic mutations. Other CTCL subtypes such as primary cutaneous anaplastic large cell lymphoma also harbor genetic alterations of the JAK\/STAT pathway in up to 50% of cases. Recently, primary cutaneous aggressive epidermotropic T-cell lymphoma, a rare fatal subtype, was found to contain a specific profile of JAK2 rearrangements. Other aggressive cytotoxic CTCL (primary cutaneous \u03b3\u03b4 T-cell lymphomas) also show genetic alterations in the JAK\/STAT pathway in a large proportion of patients. Thus, CTCL patients have a heterogeneous genetic\/transcriptional and epigenetic background, and there is no uniform treatment for these patients. In this scenario, a pathway-based personalized management is required. Cutaneous B-cell lymphoma (CBCL) subtypes present a variable genetic profile. The genetic heterogeneity parallels the multiple types of specialized B-cells and their specific tissue distribution. Particularly, many recurrent hotspot and damaging mutations in primary cutaneous diffuse large B-cell lymphoma of the leg type, involving MYD88 gene, or BCL6 and MYC translocations and BLIMP1 or CDKN2A deletions are useful for diagnostic and prognostic purposes for this aggressive subtype from other indolent CBCL forms.<\/jats:p>","DOI":"10.3390\/cancers14204972","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T22:18:13Z","timestamp":1665526693000},"page":"4972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Genetics Abnormalities with Clinical Impact in Primary Cutaneous Lymphomas"],"prefix":"10.3390","volume":"14","author":[{"given":"Fernando","family":"Gallardo","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Passeig Maritim 25-29, 08003 Barcelona, Spain"},{"name":"Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon M.","family":"Pujol","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Passeig Maritim 25-29, 08003 Barcelona, Spain"},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1182\/blood-2018-11-881268","article-title":"The 2018 update of the WHO-EORTC classifi-cation for primary cutaneous lymphomas","volume":"133","author":"Willemze","year":"2019","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee","volume":"140","author":"Campo","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dobos, G., Pohrt, A., Ram-Wolff, C., Lebb\u00e9, C., Bouaziz, J.-D., Battistella, M., Bagot, M., and De Masson, A. 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