{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:59:18Z","timestamp":1781528358835,"version":"3.54.1"},"reference-count":100,"publisher":"Harborside Press, LLC","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>Cutaneous melanoma risk assessment relies on clinicopathologic staging, which incompletely captures individual risk of nodal involvement, recurrence, and melanoma-specific mortality. Gene expression profiling (GEP) assays have been proposed to refine prognostication by measuring multigene transcriptional signatures from primary tumors. Here, we review the development, validation evidence, and limitations of the 2 most studied GEP tests for primary melanoma, and we evaluate their potential clinical utility amid rapidly evolving treatment paradigms. We highlight key knowledge gaps that should be addressed before advocating for broader GEP assay implementation.<\/jats:p>","DOI":"10.6004\/jnccn.2026.7041","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:47:55Z","timestamp":1781527675000},"page":"278-282","source":"Crossref","is-referenced-by-count":0,"title":["The Evolving Clinical Utility of Gene Expression Profiling in Cutaneous Melanoma"],"prefix":"10.6004","volume":"24","author":[{"given":"Ahmad","family":"Rajeh","sequence":"first","affiliation":[{"name":"Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Kiuru","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California Davis, Sacramento, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Nelson","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"JAMA Netw Open","first-page":"e214708","article-title":"Estimated projection of US cancer incidence and death to 2040","volume":"4","author":"Rahib L","year":"2021","unstructured":"Rahib L, Wehner MR, Matrisian LM, Nead KT. 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Melanoma Manag 2024;11:2424708."},{"key":"B5","series-title":"Methods Mol Biol","first-page":"427","article-title":"A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile","volume":"1102","author":"Harbour JW","year":"2014","unstructured":"Harbour JW. A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile. Methods Mol Biol 2014;1102:427\u2013440."},{"key":"B6","series-title":"N Engl J Med","first-page":"2005","article-title":"Prospective validation of a 21-gene expression assay in breast cancer","volume":"373","author":"Sparano JA","year":"2015","unstructured":"Sparano JA, Gray RJ, Makower DF,  Prospective validation of a 21-gene expression assay in breast cancer. 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Eur J Cancer 2025;220:115365."},{"key":"B9","series-title":"JAMA Dermatol","first-page":"866","article-title":"Association between patient age and lymph node positivity in thin melanoma","volume":"153","author":"Sinnamon AJ","year":"2017","unstructured":"Sinnamon AJ, Neuwirth MG, Yalamanchi P,  Association between patient age and lymph node positivity in thin melanoma. JAMA Dermatol 2017;153:866\u2013873."},{"key":"B10","series-title":"JAMA Surg","first-page":"260","article-title":"Population-based validation of the MIA and MSKCC tools for predicting sentinel lymph node status","volume":"159","author":"Olofsson Bagge R","year":"2024","unstructured":"Olofsson Bagge R, Mikiver R, Marchetti MA,  Population-based validation of the MIA and MSKCC tools for predicting sentinel lymph node status. JAMA Surg 2024;159:260\u2013268."},{"key":"B11","series-title":"J Am Acad Dermatol","first-page":"208","article-title":"Guidelines of care for the management of primary cutaneous melanoma","volume":"80","author":"Swetter SM","year":"2019","unstructured":"Swetter SM, Tsao H, Bichakjian CK,  Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol 2019;80:208\u2013250."},{"key":"B12","series-title":"Ann Surg Oncol","first-page":"1429","article-title":"Society of Surgical Oncology consensus statement: assessing the evidence for and utility of gene expression profiling of primary cutaneous melanoma","volume":"32","author":"Bartlett EK","year":"2025","unstructured":"Bartlett EK, O\u2019Donoghue C, Boland G,  Society of Surgical Oncology consensus statement: assessing the evidence for and utility of gene expression profiling of primary cutaneous melanoma. Ann Surg Oncol 2025;32:1429\u20131442."},{"key":"B13","article-title":"NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 1.2026","author":"Swetter SM","unstructured":"Swetter SM, Johnson D, Albertini MR,  NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 1.2026. Accessed April 6, 2026. To view the most recent version, visit https:\/\/www.nccn.org\/"},{"key":"B14","series-title":"JAMA Dermatol","first-page":"953","article-title":"Performance of gene expression profile tests for prognosis in patients with localized cutaneous melanoma: a systematic review and meta-analysis","volume":"156","author":"Marchetti MA","year":"2020","unstructured":"Marchetti MA, Coit DG, Dusza SW,  Performance of gene expression profile tests for prognosis in patients with localized cutaneous melanoma: a systematic review and meta-analysis. JAMA Dermatol 2020;156:953\u2013962."},{"key":"B15","series-title":"Eur J Cancer","first-page":"113989","article-title":"Sentinel lymph node risk prognostication in primary cutaneous melanoma through tissue-based profiling, potentially redefining the need for sentinel lymph node biopsy","volume":"202","author":"K\u00f6tt J","year":"2024","unstructured":"K\u00f6tt J, Zimmermann N, Zell T,  Sentinel lymph node risk prognostication in primary cutaneous melanoma through tissue-based profiling, potentially redefining the need for sentinel lymph node biopsy. Eur J Cancer 2024;202:113989."},{"key":"B16","series-title":"Diagn Pathol","first-page":"13","article-title":"Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients","volume":"13","author":"Cook RW","year":"2018","unstructured":"Cook RW, Middlebrook B, Wilkinson J,  Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. Diagn Pathol 2018;13:13."},{"key":"B17","series-title":"Clin Cancer Res","first-page":"175","article-title":"Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma","volume":"21","author":"Gerami P","year":"2015","unstructured":"Gerami P, Cook RW, Wilkinson J,  Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res 2015;21:175\u2013183."},{"key":"B18","series-title":"Head Neck","first-page":"827","article-title":"Performance of a prognostic 31-gene expression profile test in cutaneous melanomas of the head and neck","volume":"40","author":"Zager JS","year":"2018","unstructured":"Zager JS, Gastman BR, Leachman S. Performance of a prognostic 31-gene expression profile test in cutaneous melanomas of the head and neck. Head Neck 2018;40:827\u2013833."},{"key":"B19","series-title":"Dermatol Surg","first-page":"1494","article-title":"Estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test","volume":"44","author":"Greenhaw BN","year":"2018","unstructured":"Greenhaw BN, Zitelli JA, Brodland DG. Estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. 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