Adriana C H van Engen-van Grunsven1, Heidi V N Küsters-Vandevelde2, Joanne De Hullu3, Lucette M van Duijn4, Jos Rijntjes4, Judith V M G Bovée5, Patricia J T A Groenen4, Willeke A M Blokx4. 1. Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands. Electronic address: Ilse.vanEngen-vanGrunsven@radboudumc.nl. 2. Department of Pathology, Canisius Wilhelmina Hospital, P.O. Box 9015, Nijmegen, 6500 GS, The Netherlands. 3. Department of Obstetrics and Gynecology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands. 4. Department of Pathology, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands. 5. Department of Pathology, Leiden University Medical Center, P.O. Box 9600, Leiden, 2300 RC, The Netherlands.
Abstract
OBJECTIVE: The aim of this study was to evaluate a series of primary melanomas of the female urogenital tract for oncogenic mutations in KIT, NRAS and BRAF in order to identify patients who may be amenable to targeted therapy. METHODS: We reviewed twenty-four cases of female urogenital tract melanomas and used Sanger sequencing analysis for the detection of oncogenic mutations in exons 9, 11, 13, and 17 of KIT; exons 2 and 3 of NRAS; and exon 15 of BRAF. RESULTS: Twenty-four patients were included: fourteen vaginal melanomas, four cervical melanomas, five urethral melanomas and one vulvar melanoma. NRAS mutations (4/24, 21%) were more prevalent than KIT mutations (1/24, 4%), while BRAF mutations were absent. Three of four NRAS mutations were present in vaginal melanomas (21%), mainly affecting codon 61 (3/4). They were mutually exclusive with the KIT mutation. The KIT mutation was present in a vaginal melanoma and affected exon 17. CONCLUSIONS: Melanomas of the female urogenital tract relatively commonly harbor mutations in NRAS; this makes NRAS an interesting therapeutic target for these patients in the advanced setting. KIT mutations were rare in our study in contrast to some previous reports. We cannot exclude that anatomical site-related differences and/or population related differences in KIT mutation frequency exist within urogenital tract melanomas.
OBJECTIVE: The aim of this study was to evaluate a series of primary melanomas of the female urogenital tract for oncogenic mutations in KIT, NRAS and BRAF in order to identify patients who may be amenable to targeted therapy. METHODS: We reviewed twenty-four cases of female urogenital tract melanomas and used Sanger sequencing analysis for the detection of oncogenic mutations in exons 9, 11, 13, and 17 of KIT; exons 2 and 3 of NRAS; and exon 15 of BRAF. RESULTS: Twenty-four patients were included: fourteen vaginal melanomas, four cervical melanomas, five urethral melanomas and one vulvar melanoma. NRAS mutations (4/24, 21%) were more prevalent than KIT mutations (1/24, 4%), while BRAF mutations were absent. Three of four NRAS mutations were present in vaginal melanomas (21%), mainly affecting codon 61 (3/4). They were mutually exclusive with the KIT mutation. The KIT mutation was present in a vaginal melanoma and affected exon 17. CONCLUSIONS:Melanomas of the female urogenital tract relatively commonly harbor mutations in NRAS; this makes NRAS an interesting therapeutic target for these patients in the advanced setting. KIT mutations were rare in our study in contrast to some previous reports. We cannot exclude that anatomical site-related differences and/or population related differences in KIT mutation frequency exist within urogenital tract melanomas.
Authors: Anastasiya Atanasova Chokoeva; Georgi Tchernev; Elena Castelli; Elisabetta Orlando; Shyam B Verma; Markus Grebe; Uwe Wollina Journal: Wien Med Wochenschr Date: 2015-05-01
Authors: Oriol Yélamos; Emily A Merkel; Lauren Meldi Sholl; Bin Zhang; Sapna M Amin; Christina Y Lee; Gerta E Guitart; Jingyi Yang; Alexander T Wenzel; Christopher G Bunick; Pedram Yazdan; Jaehyuk Choi; Pedram Gerami Journal: J Invest Dermatol Date: 2016-05-21 Impact factor: 8.551