DNA methylation classes of stage II and III primary melanomas and their clinical and prognostic significance Journal Article
| Authors: | Conway, K.; Edmiston, S. N.; Vondras, A.; Reiner, A.; Corcoran, D. L.; Shen, R.; Parrish, E. A.; Hao, H.; Lin, L.; Kenney, J. M.; Ilelaboye, G.; Kostrzewa, C. E.; Kuan, P. F.; Busam, K. J.; Lezcano, C.; Lee, T. K.; Hernando, E.; Googe, P. B.; Ollila, D. W.; Moschos, S.; Gorlov, I.; Amos, C. I.; Ernstoff, M. S.; Cust, A. E.; Wilmott, J. S.; Scolyer, R. A.; Mann, G. J.; Vergara, I. A.; Ko, J.; Rees, J. R.; Yan, S.; Nagore, E.; Bosenberg, M.; Rothberg, B. G.; Osman, I.; Lee, J. E.; Saenger, Y.; Bogner, P.; Thompson, C. L.; Gerstenblith, M.; Holmen, S. L.; Funchain, P.; Brunsgaard, E.; Depcik-Smith, N. D.; Luo, L.; Boyce, T.; Orlow, I.; Begg, C. B.; Berwick, M.; Thomas, N. E.; for the InterMEL Study Group |
| Article Title: | DNA methylation classes of stage II and III primary melanomas and their clinical and prognostic significance |
| Abstract: | PURPOSEPatients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival.MATERIALS AND METHODSInterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia. Cases are patients who died of melanoma within 5 years from original diagnosis. Controls survived longer than 5 years without evidence of melanoma recurrence or relapse. Methylation classes, distinguished by consensus clustering of 850K methylation data, were evaluated for their clinicopathologic characteristics, 5-year survival status, and differentially methylated gene sets.RESULTSAmong 422 InterMEL melanomas, consensus clustering revealed three primary melanoma methylation classes (MethylClasses): A CpG island methylator phenotype (CIMP) class, an intermediate methylation (IM) class, and a low methylation (LM) class. CIMP and IM were associated with higher AJCC stage (both P =.002), Breslow thickness (CIMP P =.002; IM P =.006), and mitotic index (both P <.001) compared with LM, while IM had higher N stage than CIMP (P =.01) and LM (P =.007). CIMP and IM had a 2-fold higher likelihood of 5-year death from melanoma than LM (CIMP odds ratio [OR], 2.16 [95% CI, 1.18 to 3.96]; IM OR, 2.00 [95% CI, 1.12 to 3.58]) in a multivariable model adjusted for age, sex, log Breslow thickness, ulceration, mitotic index, and N stage. Despite more extensive CpG island hypermethylation in CIMP, CIMP and IM shared similar patterns of differential methylation and gene set enrichment compared with LM.CONCLUSIONMelanoma MethylClasses may provide clinical value in predicting 5-year death from melanoma among patients with primary melanoma independent of other clinicopathologic factors. © 2024 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer survival; controlled study; human tissue; aged; middle aged; major clinical study; case control study; clinical feature; histopathology; united states; comparative study; cancer staging; quality control; disease association; melanoma; malignant lentigo; clinical assessment; evidence based practice; relapse; retrospective study; dna methylation; dna; cpg island; population; australia; molecular biology; phenotypic variation; cutaneous melanoma; skin ulcer; mitosis index; solar elastosis; cancer prognosis; breslow thickness; human; male; female; article; cpg island methylator phenotype; gene set enrichment analysis; intermediate methylation; low methylation |
| Journal Title: | JCO Precision Oncology |
| Volume: | 8 |
| ISSN: | 2473-4284 |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2024-12-01 |
| Start Page: | 00375 |
| Language: | English |
| DOI: | 10.1200/po-24-00375 |
| PUBMED: | 39509669 |
| PROVIDER: | scopus |
| PMCID: | PMC11737429 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus |
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