TY - JOUR
T1 - DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance
AU - InterMEL Study Group
AU - Conway, Kathleen
AU - Edmiston, Sharon N.
AU - Vondras, Amanda
AU - Reiner, Allison
AU - Corcoran, David L.
AU - Shen, Ronglai
AU - Parrish, Eloise A.
AU - Hao, Honglin
AU - Lin, Lan
AU - Kenney, Jessica M.
AU - Ilelaboye, Gbemisola Elizabeth
AU - Kostrzewa, Caroline E.
AU - Kuan, Pei Fen
AU - Busam, Klaus J.
AU - Lezcano, Cecilia
AU - Lee, Tim K.
AU - Hernando, Eva
AU - Googe, Paul B.
AU - Ollila, David W.
AU - Moschos, Stergios J.
AU - Gorlov, Ivan P.
AU - Amos, Christopher I.
AU - Ernstoff, Marc S.
AU - Cust, Anne E.
AU - Wilmott, James S.
AU - Scolyer, Richard A.
AU - Mann, Graham J.
AU - Vergara, Ismael A.
AU - Ko, Jennifer S.
AU - Rees, Judy R.
AU - Yan, Shaofeng
AU - Nagore, Eduardo
AU - Bosenberg, Marcus
AU - Rothberg, Bonnie Gould E.
AU - Osman, Iman
AU - Lee, Jeffrey E.
AU - Saenger, Yvonne M.
AU - Bogner, Paul N.
AU - Thompson, Cheryl L.
AU - Gerstenblith, Meg R.
AU - Holmen, Sheri L.
AU - Funchain, Pauline
AU - Brunsgaard, Elise K.
AU - Depcik-Smith, Natalie D.
AU - Luo, Li
AU - Boyce, Tawny W.
AU - Orlow, Irene
AU - Begg, Colin B.
AU - Berwick, Marianne
AU - Thomas, Nancy E.
N1 - Publisher Copyright:
© 2024 by American Society of Clinical Oncology.
PY - 2024/11/1
Y1 - 2024/11/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85210373116
U2 - 10.1200/PO-24-00375
DO - 10.1200/PO-24-00375
M3 - Article
C2 - 39509669
AN - SCOPUS:85210373116
SN - 2473-4284
VL - 8
JO - JCO Precision Oncology
JF - JCO Precision Oncology
M1 - 00375
ER -