Dermatologic Therapy, Vol. 28, 2015, 105–106 Printed in the United States · All rights reserved
© 2014 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
JOURNAL HIGHLIGHTS
The cell of origin of acral melanomas may be hiding in the sweat glands In order to develop targeted approaches to prevent the initiation of melanoma, it is critical to understand the differentiation state and location of its cell of origin. Although it may be assumed that the origin is a differentiated melanocyte, this remains an area of active debate (1). The cell of origin may instead be a less differentiated precursor with greater proliferative potential (1). Although a niche for murine melanocyte precursors has been shown to exist in the hair follicle (2), the niche for melanocytic precursors on glabrous skin was unclear. Melanocytic precursors have been identified by KIT expression in the human hair follicle and interestingly KIT-expressing cells have also been noted in human eccrine coils – but not apocrine coils (3). Data from Dr Nishimura’s laboratory suggest that eccrine melanocytic precursor cells may be the source of acral melanomas (4). They studied genetically engineered mice that expressed a fluorescently tagged nuclear histone protein under the control of an early melanocytic DCT promoter. They were able to show that melanocytic precursor cells exist in the eccrine coils and likely migrate to the epidermis under normal conditions to replenish melanocytes. In studying human acral melanomas, they noted that the cyclin B amplifications, which are a hallmark of acral melanomas (5), are present within the unpigmented precursor melanocytic cells in
the eccrine coils. The amplifications were more marked in the epidermal melanoma cells suggesting further progression in the cells that had presumably migrated from that location. This pattern of migration is also consistent with the parallel ridge dermoscopic pattern diagnostic for acral melanomas (6). Thus, these findings may have uncloaked the hiding place for cells driving the development of acral melanoma and sets the stage for the potential development of targeted preventative therapies.
Conflict of interest Dr. Grichnik has served as a consultant for Roche, Novartis, and CaliberID. He received equipment and meeting support from CaliberID. He’s a founder and major shareholder of DigitalDerm, Inc. James M. Grichnik*† *Frankel Family Division of Melanocytic Tumors, Department of Dermatology and Cutaneous Surgery, †Melanoma Program, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
References Address correspondence and reprint requests to: James M. Grichnik, MD, PhD, Professor and Chief, Frankel Family Division of Melanocytic Tumors, Department of Dermatology and Cutaneous Surgery, Director, Melanoma Program, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Room 912, BRB, 1501 NW 10th Avenue, Miami, FL 33136, or email: [email protected].
1. Grichnik JM. Melanoma, nevogenesis, and stem cell biology. J Invest Dermatol 2008: 128: 2365–2380. 2. Nishimura EK, Jordan SA, Oshima H, et al. Dominant role of the niche in melanocyte stem-cell fate determination. Nature 2002: 416: 854–860. 3. Grichnik JM, Ali WN, Burch JA, et al. KIT expression reveals a population of precursor melanocytes in human skin. J Invest Dermatol 1996: 106: 967–971.
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Grichnik 4. Okamoto N, Aoto T, Uhara H, et al. A melanocyte-melanoma precursor niche in sweat glands of volar skin. Pigment Cell Melanoma Res 2014: 27: 1039–1050. 5. Sauter ER, Yeo UC, von Stemm A, et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res 2002: 62: 3200–3206.
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6. Phan A, Dalle S, Touzet S, Ronger-Savle S, Balme B, Thomas L. Dermoscopic features of acral lentiginous melanoma in a large series of 110 cases in a white population. Br J Dermatol 2010: 162: 765–771.
© 2014 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
JOURNAL HIGHLIGHTS
The cell of origin of acral melanomas may be hiding in the sweat glands In order to develop targeted approaches to prevent the initiation of melanoma, it is critical to understand the differentiation state and location of its cell of origin. Although it may be assumed that the origin is a differentiated melanocyte, this remains an area of active debate (1). The cell of origin may instead be a less differentiated precursor with greater proliferative potential (1). Although a niche for murine melanocyte precursors has been shown to exist in the hair follicle (2), the niche for melanocytic precursors on glabrous skin was unclear. Melanocytic precursors have been identified by KIT expression in the human hair follicle and interestingly KIT-expressing cells have also been noted in human eccrine coils – but not apocrine coils (3). Data from Dr Nishimura’s laboratory suggest that eccrine melanocytic precursor cells may be the source of acral melanomas (4). They studied genetically engineered mice that expressed a fluorescently tagged nuclear histone protein under the control of an early melanocytic DCT promoter. They were able to show that melanocytic precursor cells exist in the eccrine coils and likely migrate to the epidermis under normal conditions to replenish melanocytes. In studying human acral melanomas, they noted that the cyclin B amplifications, which are a hallmark of acral melanomas (5), are present within the unpigmented precursor melanocytic cells in
the eccrine coils. The amplifications were more marked in the epidermal melanoma cells suggesting further progression in the cells that had presumably migrated from that location. This pattern of migration is also consistent with the parallel ridge dermoscopic pattern diagnostic for acral melanomas (6). Thus, these findings may have uncloaked the hiding place for cells driving the development of acral melanoma and sets the stage for the potential development of targeted preventative therapies.
Conflict of interest Dr. Grichnik has served as a consultant for Roche, Novartis, and CaliberID. He received equipment and meeting support from CaliberID. He’s a founder and major shareholder of DigitalDerm, Inc. James M. Grichnik*† *Frankel Family Division of Melanocytic Tumors, Department of Dermatology and Cutaneous Surgery, †Melanoma Program, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
References Address correspondence and reprint requests to: James M. Grichnik, MD, PhD, Professor and Chief, Frankel Family Division of Melanocytic Tumors, Department of Dermatology and Cutaneous Surgery, Director, Melanoma Program, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Room 912, BRB, 1501 NW 10th Avenue, Miami, FL 33136, or email: [email protected].
1. Grichnik JM. Melanoma, nevogenesis, and stem cell biology. J Invest Dermatol 2008: 128: 2365–2380. 2. Nishimura EK, Jordan SA, Oshima H, et al. Dominant role of the niche in melanocyte stem-cell fate determination. Nature 2002: 416: 854–860. 3. Grichnik JM, Ali WN, Burch JA, et al. KIT expression reveals a population of precursor melanocytes in human skin. J Invest Dermatol 1996: 106: 967–971.
105
Grichnik 4. Okamoto N, Aoto T, Uhara H, et al. A melanocyte-melanoma precursor niche in sweat glands of volar skin. Pigment Cell Melanoma Res 2014: 27: 1039–1050. 5. Sauter ER, Yeo UC, von Stemm A, et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res 2002: 62: 3200–3206.
106
6. Phan A, Dalle S, Touzet S, Ronger-Savle S, Balme B, Thomas L. Dermoscopic features of acral lentiginous melanoma in a large series of 110 cases in a white population. Br J Dermatol 2010: 162: 765–771.
