DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance

Kathleen Conway; Sharon N. Edmiston; Amanda Vondras; Allison Reiner; David L. Corcoran; Ronglai Shen; Eloise A. Parrish; Honglin Hao; Lan Lin; Jessica M. Kenney; Gbemisola Ilelaboye; Caroline E. Kostrzewa; Pei Fen Kuan; Klaus J. Busam; Cecilia Lezcano; Tim K. Lee; Eva Hernando; Paul B. Googe; David W. Ollila; Stergios Moschos; Ivan Gorlov; Christopher I. Amos; Marc S. Ernstoff; Anne E. Cust; James S. Wilmott; Richard A. Scolyer; Graham J. Mann; Ismael A. Vergara; Jennifer Ko; Judy R. Rees; Shaofeng Yan; Eduardo Nagore; Marcus Bosenberg; Bonnie Gould Rothberg; Iman Osman; Jeffrey E. Lee; Yvonne Saenger; Paul Bogner; Cheryl L. Thompson; Meg Gerstenblith; Sheri L. Holmen; Pauline Funchain; Elise Brunsgaard; Natalie D. Depcik-Smith; Li Luo; Tawny Boyce; Irene Orlow; Colin B. Begg; Marianne Berwick; Nancy E. Thomas; Marianne Berwick; Li Luo; Tawny W. Boyce; Adam Z. Reynolds; Charles Wiggins; Nancy E. Thomas; Kathleen Conway; Sharon N. Edmiston; David W. Ollila; Honglin Hao; Eloise Parrish; Paul B. Googe; Stergios J. Moschos; David Corcoran; Amanda Vondras; Yihsuan S. Tsai; Lan Lin; Ronglai Shen; Colin B. Begg; Arshi Arora; Venkatraman Seshan; Allie Reiner; Caroline E. Kostrzewa; Klaus J. Busam; Irene Orlow; Cecilia Lezcano; Jessica M. Kenney; Keimya D. Sadeghi; Kelli O'connell; Gbemisola Elizabeth Ilelaboye; Heta Parmar; Siok Leong; Sergio Corrales; Richard A. Scolyer; Anne E. Cust; James S. Wilmott; Graham J. Mann; Ping Shang; Hazel Burke; Peter M. Ferguson; Valerie Jakrot; Tim K. Lee; Eva Hernando; Iman Osman; Douglas Hanniford; Diana Argibay; Una Moran; Adriana Heguy; Sitharam Ramaswami; Christopher I. Amos; Ivan P. Gorlov; Dakai Zhu; Marc Ernstoff; Paul N. Bogner; Jeffrey E. Lee; Judy R. Rees; Shaofeng Yan; Meg R. Gerstenblith; Cheryl Thompson; Jennifer S. Ko; Pauline Funchain; Peter Ngo; Marcus Bosenberg; Bonnie E. Gould Rothberg; Gauri Panse; Yvonne M. Saenger; Benjamin T. Fullerton; Sheri L. Holmen; Howard Colman; Elise K. Brunsgaard; David Wada; Eduardo Nagore; Esperanza Manrique-Silva; Celia Requena; Victor Traves; David Millan-Esteban; Michelle Rainka

doi:10.1200/PO-24-00375

DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance

Kathleen Conway, Sharon N. Edmiston, Amanda Vondras, Allison Reiner, David L. Corcoran, Ronglai Shen, Eloise A. Parrish, Honglin Hao, Lan Lin, Jessica M. Kenney, Gbemisola Ilelaboye, Caroline E. Kostrzewa, Pei Fen Kuan, Klaus J. Busam, Cecilia Lezcano, Tim K. Lee, Eva Hernando, Paul B. Googe, David W. Ollila, Stergios MoschosIvan Gorlov, Christopher I. Amos, Marc S. Ernstoff, Anne E. Cust, James S. Wilmott, Richard A. Scolyer, Graham J. Mann, Ismael A. Vergara, Jennifer Ko, Judy R. Rees, Shaofeng Yan, Eduardo Nagore, Marcus Bosenberg, Bonnie Gould Rothberg, Iman Osman, Jeffrey E. Lee, Yvonne Saenger, Paul Bogner, Cheryl L. Thompson, Meg Gerstenblith, Sheri L. Holmen, Pauline Funchain, Elise Brunsgaard, Natalie D. Depcik-Smith, Li Luo, Tawny Boyce, Irene Orlow, Colin B. Begg, Marianne Berwick, Nancy E. Thomas, Marianne Berwick, Li Luo, Tawny W. Boyce, Adam Z. Reynolds, Charles Wiggins, Nancy E. Thomas, Kathleen Conway, Sharon N. Edmiston, David W. Ollila, Honglin Hao, Eloise Parrish, Paul B. Googe, Stergios J. Moschos, David Corcoran, Amanda Vondras, Yihsuan S. Tsai, Lan Lin, Ronglai Shen, Colin B. Begg, Arshi Arora, Venkatraman Seshan, Allie Reiner, Caroline E. Kostrzewa, Klaus J. Busam, Irene Orlow, Cecilia Lezcano, Jessica M. Kenney, Keimya D. Sadeghi, Kelli O'connell, Gbemisola Elizabeth Ilelaboye, Heta Parmar, Siok Leong, Sergio Corrales, Richard A. Scolyer, Anne E. Cust, James S. Wilmott, Graham J. Mann, Ping Shang, Hazel Burke, Peter M. Ferguson, Valerie Jakrot, Tim K. Lee, Eva Hernando, Iman Osman, Douglas Hanniford, Diana Argibay, Una Moran, Adriana Heguy, Sitharam Ramaswami, Christopher I. Amos, Ivan P. Gorlov, Dakai Zhu, Marc Ernstoff, Paul N. Bogner, Jeffrey E. Lee, Judy R. Rees, Shaofeng Yan, Meg R. Gerstenblith, Cheryl Thompson, Jennifer S. Ko, Pauline Funchain, Peter Ngo, Marcus Bosenberg, Bonnie E. Gould Rothberg, Gauri Panse, Yvonne M. Saenger, Benjamin T. Fullerton, Sheri L. Holmen, Howard Colman, Elise K. Brunsgaard, David Wada, Eduardo Nagore, Esperanza Manrique-Silva, Celia Requena, Victor Traves, David Millan-Esteban, Michelle Rainka

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	00375
Journal	JCO Precision Oncology
Volume	8
DOIs	https://doi.org/10.1200/PO-24-00375
State	Published - Nov 1 2024

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1200/PO-24-00375

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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., ... Rainka, M. (2024). DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance. JCO Precision Oncology, 8, Article 00375. https://doi.org/10.1200/PO-24-00375

@article{c4932976e11f476292065a68866c37cf,

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.",

author = "Kathleen Conway and Edmiston, {Sharon N.} and Amanda Vondras and Allison Reiner and Corcoran, {David L.} and Ronglai Shen and Parrish, {Eloise A.} and Honglin Hao and Lan Lin and Kenney, {Jessica M.} and Gbemisola Ilelaboye and Kostrzewa, {Caroline E.} and Kuan, {Pei Fen} and Busam, {Klaus J.} and Cecilia Lezcano and Lee, {Tim K.} and Eva Hernando and Googe, {Paul B.} and Ollila, {David W.} and Stergios Moschos and Ivan Gorlov and Amos, {Christopher I.} and Ernstoff, {Marc S.} and Cust, {Anne E.} and Wilmott, {James S.} and Scolyer, {Richard A.} and Mann, {Graham J.} and Vergara, {Ismael A.} and Jennifer Ko and Rees, {Judy R.} and Shaofeng Yan and Eduardo Nagore and Marcus Bosenberg and Rothberg, {Bonnie Gould} and Iman Osman and Lee, {Jeffrey E.} and Yvonne Saenger and Paul Bogner and Thompson, {Cheryl L.} and Meg Gerstenblith and Holmen, {Sheri L.} and Pauline Funchain and Elise Brunsgaard and Depcik-Smith, {Natalie D.} and Li Luo and Tawny Boyce and Irene Orlow and Begg, {Colin B.} and Marianne Berwick and Thomas, {Nancy E.} and Marianne Berwick and Li Luo and Boyce, {Tawny W.} and Reynolds, {Adam Z.} and Charles Wiggins and Thomas, {Nancy E.} and Kathleen Conway and Edmiston, {Sharon N.} and Ollila, {David W.} and Honglin Hao and Eloise Parrish and Googe, {Paul B.} and Moschos, {Stergios J.} and David Corcoran and Amanda Vondras and Tsai, {Yihsuan S.} and Lan Lin and Ronglai Shen and Begg, {Colin B.} and Arshi Arora and Venkatraman Seshan and Allie Reiner and Kostrzewa, {Caroline E.} and Busam, {Klaus J.} and Irene Orlow and Cecilia Lezcano and Kenney, {Jessica M.} and Sadeghi, {Keimya D.} and Kelli O'connell and Ilelaboye, {Gbemisola Elizabeth} and Heta Parmar and Siok Leong and Sergio Corrales and Scolyer, {Richard A.} and Cust, {Anne E.} and Wilmott, {James S.} and Mann, {Graham J.} and Ping Shang and Hazel Burke and Ferguson, {Peter M.} and Valerie Jakrot and Lee, {Tim K.} and Eva Hernando and Iman Osman and Douglas Hanniford and Diana Argibay and Una Moran and Adriana Heguy and Sitharam Ramaswami and Amos, {Christopher I.} and Gorlov, {Ivan P.} and Dakai Zhu and Marc Ernstoff and Bogner, {Paul N.} and Lee, {Jeffrey E.} and Rees, {Judy R.} and Shaofeng Yan and Gerstenblith, {Meg R.} and Cheryl Thompson and Ko, {Jennifer S.} and Pauline Funchain and Peter Ngo and Marcus Bosenberg and {Gould Rothberg}, {Bonnie E.} and Gauri Panse and Saenger, {Yvonne M.} and Fullerton, {Benjamin T.} and Holmen, {Sheri L.} and Howard Colman and Brunsgaard, {Elise K.} and David Wada and Eduardo Nagore and Esperanza Manrique-Silva and Celia Requena and Victor Traves and David Millan-Esteban and Michelle Rainka",

note = "Publisher Copyright: {\textcopyright} 2024 by American Society of Clinical Oncology.",

year = "2024",

month = nov,

day = "1",

doi = "10.1200/PO-24-00375",

language = "English (US)",

volume = "8",

journal = "JCO Precision Oncology",

issn = "2473-4284",

publisher = "Lippincott Williams and Wilkins",

}

Conway, K, Edmiston, SN, Vondras, A, Reiner, A, Corcoran, DL, Shen, R, Parrish, EA, Hao, H, Lin, L, Kenney, JM, Ilelaboye, G, Kostrzewa, CE, Kuan, PF, Busam, KJ, Lezcano, C, Lee, TK, Hernando, E, Googe, PB, Ollila, DW, Moschos, S, Gorlov, I, Amos, CI, Ernstoff, MS, Cust, AE, Wilmott, JS, Scolyer, RA, Mann, GJ, Vergara, IA, Ko, J, Rees, JR, Yan, S, Nagore, E, Bosenberg, M, Rothberg, BG, Osman, I, Lee, JE, Saenger, Y, Bogner, P, Thompson, CL, Gerstenblith, M, Holmen, SL, Funchain, P, Brunsgaard, E, Depcik-Smith, ND, Luo, L, Boyce, T, Orlow, I, Begg, CB, Berwick, M, Thomas, NE, Berwick, M, Luo, L, Boyce, TW, Reynolds, AZ, Wiggins, C, Thomas, NE, Conway, K, Edmiston, SN, Ollila, DW, Hao, H, Parrish, E, Googe, PB, Moschos, SJ, Corcoran, D, Vondras, A, Tsai, YS, Lin, L, Shen, R, Begg, CB, Arora, A, Seshan, V, Reiner, A, Kostrzewa, CE, Busam, KJ, Orlow, I, Lezcano, C, Kenney, JM, Sadeghi, KD, O'connell, K, Ilelaboye, GE, Parmar, H, Leong, S, Corrales, S, Scolyer, RA, Cust, AE, Wilmott, JS, Mann, GJ, Shang, P, Burke, H, Ferguson, PM, Jakrot, V, Lee, TK, Hernando, E, Osman, I, Hanniford, D, Argibay, D, Moran, U, Heguy, A, Ramaswami, S, Amos, CI, Gorlov, IP, Zhu, D, Ernstoff, M, Bogner, PN, Lee, JE, Rees, JR, Yan, S, Gerstenblith, MR, Thompson, C, Ko, JS, Funchain, P, Ngo, P, Bosenberg, M, Gould Rothberg, BE, Panse, G, Saenger, YM, Fullerton, BT, Holmen, SL, Colman, H, Brunsgaard, EK, Wada, D, Nagore, E, Manrique-Silva, E, Requena, C, Traves, V, Millan-Esteban, D & Rainka, M 2024, 'DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance', JCO Precision Oncology, vol. 8, 00375. https://doi.org/10.1200/PO-24-00375

TY - JOUR

T1 - DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance

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

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

AU - Gorlov, Ivan

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

AU - Rees, Judy R.

AU - Yan, Shaofeng

AU - Nagore, Eduardo

AU - Bosenberg, Marcus

AU - Rothberg, Bonnie Gould

AU - Osman, Iman

AU - Lee, Jeffrey E.

AU - Saenger, Yvonne

AU - Bogner, Paul

AU - Thompson, Cheryl L.

AU - Gerstenblith, Meg

AU - Holmen, Sheri L.

AU - Funchain, Pauline

AU - Brunsgaard, Elise

AU - Depcik-Smith, Natalie D.

AU - Luo, Li

AU - Boyce, Tawny

AU - Orlow, Irene

AU - Begg, Colin B.

AU - Berwick, Marianne

AU - Thomas, Nancy E.

AU - Berwick, Marianne

AU - Luo, Li

AU - Boyce, Tawny W.

AU - Reynolds, Adam Z.

AU - Wiggins, Charles

AU - Thomas, Nancy E.

AU - Conway, Kathleen

AU - Edmiston, Sharon N.

AU - Ollila, David W.

AU - Hao, Honglin

AU - Parrish, Eloise

AU - Googe, Paul B.

AU - Moschos, Stergios J.

AU - Corcoran, David

AU - Vondras, Amanda

AU - Tsai, Yihsuan S.

AU - Lin, Lan

AU - Shen, Ronglai

AU - Begg, Colin B.

AU - Arora, Arshi

AU - Seshan, Venkatraman

AU - Reiner, Allie

AU - Kostrzewa, Caroline E.

AU - Busam, Klaus J.

AU - Orlow, Irene

AU - Lezcano, Cecilia

AU - Kenney, Jessica M.

AU - Sadeghi, Keimya D.

AU - O'connell, Kelli

AU - Ilelaboye, Gbemisola Elizabeth

AU - Parmar, Heta

AU - Leong, Siok

AU - Corrales, Sergio

AU - Scolyer, Richard A.

AU - Cust, Anne E.

AU - Wilmott, James S.

AU - Mann, Graham J.

AU - Shang, Ping

AU - Burke, Hazel

AU - Ferguson, Peter M.

AU - Jakrot, Valerie

AU - Lee, Tim K.

AU - Hernando, Eva

AU - Osman, Iman

AU - Hanniford, Douglas

AU - Argibay, Diana

AU - Moran, Una

AU - Heguy, Adriana

AU - Ramaswami, Sitharam

AU - Amos, Christopher I.

AU - Gorlov, Ivan P.

AU - Zhu, Dakai

AU - Ernstoff, Marc

AU - Bogner, Paul N.

AU - Lee, Jeffrey E.

AU - Rees, Judy R.

AU - Yan, Shaofeng

AU - Gerstenblith, Meg R.

AU - Thompson, Cheryl

AU - Ko, Jennifer S.

AU - Funchain, Pauline

AU - Ngo, Peter

AU - Bosenberg, Marcus

AU - Gould Rothberg, Bonnie E.

AU - Panse, Gauri

AU - Saenger, Yvonne M.

AU - Fullerton, Benjamin T.

AU - Holmen, Sheri L.

AU - Colman, Howard

AU - Brunsgaard, Elise K.

AU - Wada, David

AU - Nagore, Eduardo

AU - Manrique-Silva, Esperanza

AU - Requena, Celia

AU - Traves, Victor

AU - Millan-Esteban, David

AU - Rainka, Michelle

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 - http://www.scopus.com/inward/record.url?scp=85210373116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85210373116&partnerID=8YFLogxK

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 -

DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance

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