Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study Journal Article
| Authors: | Luo, L.; Shen, R.; Arora, A.; Orlow, I.; Busam, K. J.; Lezcano, C.; Lee, T. K.; Hernando, E.; Gorlov, I.; Amos, C.; Ernstoff, M. S.; Seshan, V. E.; Cust, A. E.; Wilmott, J.; Scolyer, R.; Mann, G.; Nagore, E.; Funchain, P.; Ko, J.; Ngo, P.; Edmiston, S. N.; Conway, K.; Googe, P. B.; Ollila, D.; Lee, J. E.; Fang, S.; Rees, J. R.; Thompson, C. L.; Gerstenblith, M.; Bosenberg, M.; Gould Rothberg, B.; Osman, I.; Saenger, Y.; Reynolds, A. Z.; Schwartz, M.; Boyce, T.; Holmen, S.; Brunsgaard, E.; Bogner, P.; Kuan, P. F.; Wiggins, C.; Thomas, N.; Begg, C. B.; Berwick, M.; InterMel |
| Article Title: | Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study |
| Abstract: | It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors. © 2022 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd. |
| Keywords: | adult; controlled study; human tissue; middle aged; unclassified drug; gene mutation; human cell; major clinical study; histopathology; cancer staging; tumor associated leukocyte; cancer immunotherapy; microrna; nevus; protein; gene frequency; protein p53; dna; telomerase reverse transcriptase; genomics; cyclin dependent kinase inhibitor 2a; prognostic models; melanocortin 1 receptor; b raf kinase; head and neck tumor; perineural invasion; cutaneous melanoma; nras protein; rna methylation; solar elastosis; human; male; female; article; nf1 protein; primary melanoma; preliminary data; protein fingerprinting; multiomics; multi-omic profiling; tumor mutations; arid2 protein |
| Journal Title: | Pigment Cell & Melanoma Research |
| Volume: | 35 |
| Issue: | 6 |
| ISSN: | 1755-1471 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2022-11-01 |
| Start Page: | 605 |
| End Page: | 612 |
| Language: | English |
| DOI: | 10.1111/pcmr.13058 |
| PUBMED: | 35876628 |
| PROVIDER: | scopus |
| PMCID: | PMC9640183 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |
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