Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)

Ifeoma U. Perkins; Serena Y. Tan; Timothy H. McCalmont; Pauline M. Chou; Thaddeus W. Mully; Pedram Gerami; Jason H. Pomerantz; Miguel Reyes-Múgica; Daniel M. Balkin; Lacey L. Kruse; Benjamin Huang; Jennifer L. Reichek; Noopur Gangopadhyay; Simon Chiosea; Jared R. Green; Sarah L. Chamlin; Ilona J. Frieden; Boris C. Bastian; Iwei Yeh

doi:10.1111/pcmr.13115

Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)

Ifeoma U. Perkins, Serena Y. Tan, Timothy H. McCalmont, Pauline M. Chou, Thaddeus W. Mully, Pedram Gerami, Jason H. Pomerantz, Miguel Reyes-Múgica, Daniel M. Balkin, Lacey L. Kruse, Benjamin Huang, Jennifer L. Reichek, Noopur Gangopadhyay, Simon Chiosea, Jared R. Green, Sarah L. Chamlin, Ilona J. Frieden, Boris C. Bastian, Iwei Yeh^*

^*Corresponding author for this work

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

4 Scopus citations

Abstract

We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.

Original language	English (US)
Pages (from-to)	6-14
Number of pages	9
Journal	Pigment Cell and Melanoma Research
Volume	37
Issue number	1
DOIs	https://doi.org/10.1111/pcmr.13115
State	Published - Jan 2024

Funding

The authors would like to acknowledge Cynthia Curry, MD and Jamie D. Aquino. This work was supported by the National Cancer Institute at the National Institutes of Health (grant number 1R35CA220481).

Keywords

ZEB2::ALK rearrangements
alk fusion genes
alk kinase inhibitors
giant congenital melanocytic nevi
pediatric melanoma

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Dermatology
Oncology

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10.1111/pcmr.13115

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Perkins, I. U., Tan, S. Y., McCalmont, T. H., Chou, P. M., Mully, T. W., Gerami, P., Pomerantz, J. H., Reyes-Múgica, M., Balkin, D. M., Kruse, L. L., Huang, B., Reichek, J. L., Gangopadhyay, N., Chiosea, S., Green, J. R., Chamlin, S. L., Frieden, I. J., Bastian, B. C., & Yeh, I. (2024). Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK). Pigment Cell and Melanoma Research, 37(1), 6-14. https://doi.org/10.1111/pcmr.13115

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title = "Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)",

abstract = "We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.",

keywords = "ZEB2::ALK rearrangements, alk fusion genes, alk kinase inhibitors, giant congenital melanocytic nevi, pediatric melanoma",

author = "Perkins, {Ifeoma U.} and Tan, {Serena Y.} and McCalmont, {Timothy H.} and Chou, {Pauline M.} and Mully, {Thaddeus W.} and Pedram Gerami and Pomerantz, {Jason H.} and Miguel Reyes-M{\'u}gica and Balkin, {Daniel M.} and Kruse, {Lacey L.} and Benjamin Huang and Reichek, {Jennifer L.} and Noopur Gangopadhyay and Simon Chiosea and Green, {Jared R.} and Chamlin, {Sarah L.} and Frieden, {Ilona J.} and Bastian, {Boris C.} and Iwei Yeh",

note = "Publisher Copyright: {\textcopyright} 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2024",

month = jan,

doi = "10.1111/pcmr.13115",

language = "English (US)",

volume = "37",

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Perkins, IU, Tan, SY, McCalmont, TH, Chou, PM, Mully, TW, Gerami, P, Pomerantz, JH, Reyes-Múgica, M, Balkin, DM, Kruse, LL, Huang, B, Reichek, JL , Gangopadhyay, N, Chiosea, S, Green, JR , Chamlin, SL, Frieden, IJ, Bastian, BC & Yeh, I 2024, 'Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)', Pigment Cell and Melanoma Research, vol. 37, no. 1, pp. 6-14. https://doi.org/10.1111/pcmr.13115

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T1 - Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)

AU - Perkins, Ifeoma U.

AU - Tan, Serena Y.

AU - McCalmont, Timothy H.

AU - Chou, Pauline M.

AU - Mully, Thaddeus W.

AU - Gerami, Pedram

AU - Pomerantz, Jason H.

AU - Reyes-Múgica, Miguel

AU - Balkin, Daniel M.

AU - Kruse, Lacey L.

AU - Huang, Benjamin

AU - Reichek, Jennifer L.

AU - Gangopadhyay, Noopur

AU - Chiosea, Simon

AU - Green, Jared R.

AU - Chamlin, Sarah L.

AU - Frieden, Ilona J.

AU - Bastian, Boris C.

AU - Yeh, Iwei

PY - 2024/1

Y1 - 2024/1

N2 - We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.

AB - We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.

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JF - Pigment Cell and Melanoma Research

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ER -

Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)

Abstract

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Keywords

ASJC Scopus subject areas

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