Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

Alexandra M. Haugh, Bin Zhang, Victor L. Quan, Erin M. Garfield, Jeffrey A. Bubley, Emily Kudalkar, Anna Elisa Verzi, Kara Walton, Timothy VandenBoom, Emily A. Merkel, Christina Y. Lee, Timothy Tan, Maria Cristina Isales, Betty Y. Kong, Alexander T. Wenzel, Christopher G. Bunick, Jaehyuk Choi, Jeffrey Alan Sosman, Pedram Gerami*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.

Original languageEnglish (US)
Pages (from-to)384-393
Number of pages10
JournalJournal of Investigative Dermatology
Volume138
Issue number2
DOIs
StatePublished - Feb 1 2018

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Cyclin D1
Solar System
Aberrations
Sun
Melanoma
Skin
Extremities
Mutation
Nevus
Sample Size

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Haugh, A. M., Zhang, B., Quan, V. L., Garfield, E. M., Bubley, J. A., Kudalkar, E., ... Gerami, P. (2018). Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure. Journal of Investigative Dermatology, 138(2), 384-393. https://doi.org/10.1016/j.jid.2017.08.022
Haugh, Alexandra M. ; Zhang, Bin ; Quan, Victor L. ; Garfield, Erin M. ; Bubley, Jeffrey A. ; Kudalkar, Emily ; Verzi, Anna Elisa ; Walton, Kara ; VandenBoom, Timothy ; Merkel, Emily A. ; Lee, Christina Y. ; Tan, Timothy ; Isales, Maria Cristina ; Kong, Betty Y. ; Wenzel, Alexander T. ; Bunick, Christopher G. ; Choi, Jaehyuk ; Sosman, Jeffrey Alan ; Gerami, Pedram. / Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 2. pp. 384-393.
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abstract = "Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67{\%}) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.",
author = "Haugh, {Alexandra M.} and Bin Zhang and Quan, {Victor L.} and Garfield, {Erin M.} and Bubley, {Jeffrey A.} and Emily Kudalkar and Verzi, {Anna Elisa} and Kara Walton and Timothy VandenBoom and Merkel, {Emily A.} and Lee, {Christina Y.} and Timothy Tan and Isales, {Maria Cristina} and Kong, {Betty Y.} and Wenzel, {Alexander T.} and Bunick, {Christopher G.} and Jaehyuk Choi and Sosman, {Jeffrey Alan} and Pedram Gerami",
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Haugh, AM, Zhang, B, Quan, VL, Garfield, EM, Bubley, JA, Kudalkar, E, Verzi, AE, Walton, K, VandenBoom, T, Merkel, EA, Lee, CY, Tan, T, Isales, MC, Kong, BY, Wenzel, AT, Bunick, CG, Choi, J, Sosman, JA & Gerami, P 2018, 'Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure', Journal of Investigative Dermatology, vol. 138, no. 2, pp. 384-393. https://doi.org/10.1016/j.jid.2017.08.022

Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure. / Haugh, Alexandra M.; Zhang, Bin; Quan, Victor L.; Garfield, Erin M.; Bubley, Jeffrey A.; Kudalkar, Emily; Verzi, Anna Elisa; Walton, Kara; VandenBoom, Timothy; Merkel, Emily A.; Lee, Christina Y.; Tan, Timothy; Isales, Maria Cristina; Kong, Betty Y.; Wenzel, Alexander T.; Bunick, Christopher G.; Choi, Jaehyuk; Sosman, Jeffrey Alan; Gerami, Pedram.

In: Journal of Investigative Dermatology, Vol. 138, No. 2, 01.02.2018, p. 384-393.

Research output: Contribution to journalArticle

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T1 - Distinct Patterns of Acral Melanoma Based on Site and Relative Sun Exposure

AU - Haugh, Alexandra M.

AU - Zhang, Bin

AU - Quan, Victor L.

AU - Garfield, Erin M.

AU - Bubley, Jeffrey A.

AU - Kudalkar, Emily

AU - Verzi, Anna Elisa

AU - Walton, Kara

AU - VandenBoom, Timothy

AU - Merkel, Emily A.

AU - Lee, Christina Y.

AU - Tan, Timothy

AU - Isales, Maria Cristina

AU - Kong, Betty Y.

AU - Wenzel, Alexander T.

AU - Bunick, Christopher G.

AU - Choi, Jaehyuk

AU - Sosman, Jeffrey Alan

AU - Gerami, Pedram

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N2 - Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.

AB - Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n = 21), volar (n = 9), and subungual/interdigital (n = 13) acral skin as well as acral nevi (n = 24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared with volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (P = 0.01), were significantly less likely to have the superficial spreading histologic subtype (P = 0.01), occurred in older patients (P = 0.05), and had more frequent involvement in non-Caucasians (P = 0.01). These differences can be explained by differing levels of UV exposure. Subungual/interdigital melanomas had the most diverse group of oncogenic mutations including PIK3CA (2/13), STK11 (2/13), EGFR (1/13), FGFR3 (1/13), and PTPN11 (1/13). In addition, subungual/interdigital melanomas had a significantly higher frequency of copy number aberrations (67%) than other subgroups (P = 0.02), particularly in CDK4 and cyclin D1, and were less likely to have BRAF mutations or a superficial spreading histologic subtype (P = 0.05) compared with volar acral melanomas. Although based on a limited sample size, differences between volar and subungual/interdigital melanomas in our study may be the result of differing levels of UV exposure.

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