{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:26:29Z","timestamp":1792707989559,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent high\u2010throughput sequencing studies have revealed frequent CDK4 and TERT amplification in mucosal melanoma, suggesting that they are potential therapeutic targets. In this study, we investigated the statuses of CDK4 and TERT in head and neck mucosal melanoma (HNMM) with the aim of providing preclinical data to support future clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In total, 29 HNMM samples were collected, including 16 oral mucosal melanoma (OMM) samples and 13 nasal cavity\/sinuses melanoma (SNMM) samples. Fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization was used to analyze CDK4 and TERT amplification, and immunohistochemistry was used to analyze CDK4 and TERT protein expression patterns. CDK4 expression was knocked down in the ME cells (an OMM cell line), and changes in cell cycle were analyzed. Cell viability assays were performed to determine the sensitivity of ME to abemaciclib (a CDK4 inhibitor) combined with dacarbazine (an anti\u2010melanoma chemotherapy drug).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We detected five samples exhibited CDK4 amplifications and nine samples exhibited TERT amplifications in our HNMM series, and found that CDK4 amplification tended to occur in combination with TERT amplification. Amplifications of CDK4 and TERT were more common in OMM than in SNMM. Amplifications of CDK4 and TERT were associated with greater CDK4 and TERT protein expression levels. CDK4 knockdown led to delayed G1\/S phase transition in ME cells. Furthermore, ME cells were sensitive to abemaciclib (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u00a0=\u00a05.23\u00a0nM). Abemaciclib and dacarbazine synergistically inhibited ME cells\u2019 viability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We confirmed high frequencies of CDK4 and TERT amplification in OMM. Combined therapy with a CDK4\/6 inhibitor and anti\u2010melanoma chemotherapeutic agents will be a reasonable strategy for future clinical trials concerning unresectable or metastatic OMM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.13180","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T08:41:59Z","timestamp":1617352919000},"page":"971-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CDK4 and TERT amplification in head and neck mucosal melanoma"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-8687","authenticated-orcid":false,"given":"Jiong","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Stomatology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwen","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry Affiliated Stomatology Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengdong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010head and Neck Oncology Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Stomatology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.03.042"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12526"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.07.017"},{"key":"e_1_2_9_5_1","first-page":"1071","article-title":"Cutaneous melanoma: from pathogenesis to therapy (Review)","volume":"52","author":"Leonardi GC","year":"2018","journal-title":"Int J Oncol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1771986"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.05.031"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22628"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12358"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5017"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3442"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11107-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(00)00116-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2061"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13767"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh296"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.07.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-388298"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0264"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0095"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2898"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-1987-z"}],"container-title":["Journal of Oral Pathology &amp; 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