Recurrent KRAS, KIT and SF3B1 mutations in melanoma of the female genital tract
Open Access
- 8 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 21 (1), 1-9
- https://doi.org/10.1186/s12885-021-08427-x
Abstract
Background Malignant melanoma of the female genital tract is relatively uncommon and accounts for 3–7% of all melanoma localizations. This study aimed to identify driver genes in melanoma of the female genital tract with the purpose of enhancing understanding of disease pathogenesis and identifying potential new therapeutic targets to develop effective therapies. Methods KIT (CD117) and BRAF expression were detected immunohistochemically. Polymerase Chain Reaction (PCR) and Sanger sequencing techniques were performed to identify the mutational status of BRAF, NRAS, KRAS, NF1, KIT, PDGFRA and SF3B1 on 19 melanomas of the female genital tract, paired with 25 cutaneous melanomas, 18 acral melanomas and 11 melanomas of nasal cavity. Results Somatic variant analysis identified KRAS (6/19; 32%) as the most commonly mutated gene, followed by KIT (4/19; 21%), SF3B1 (3/19; 16%) and NRAS (1/19; 5%). None of the cases were found to harbor BRAF, NF1 and PDGFRA mutations in melanomas of the female genital tract. However, none of the cases were found to harbor SF3B1 and KIT mutations in cutaneous melanomas, acral melanomas and melanomas of nasal cavity. Recurrent KIT mutations, as well as mutations in the less frequently mutated genes NRAS and SF3B1, were exclusively detected in vulvovaginal melanomas, but not in tumors arising in the cervix. However, recurrent KRAS mutations were detected in similar frequencies in tumors of the vulva, vagina, and cervix. Additionally, recurrent KRAS and KIT mutations occurred predominantly in polygonal and epithelioid cell types of melanoma in the female genital tract. Immunohistochemistry revealed moderate or strong cytoplasmic CD117 expression in 6 of the 19 cases (31.6%). Conclusions We observed that gynecologic melanoma harbored distinct mutation rates in the KIT, BRAF, SF3B1, KRAS, and NRAS genes. Our findings support the notion that gynecologic melanoma is a distinct entity from non-gynecologic melanoma, and these findings offer insights into future therapeutic options for these patients.Keywords
This publication has 38 references indexed in Scilit:
- Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanomaCancer, 2016
- NRAS mutations are more prevalent than KIT mutations in melanoma of the female urogenital tract—A study of 24 cases from the NetherlandsGynecologic Oncology, 2014
- Efficacy and safety of ipilimumab 3mg/kg in patients with pretreated, metastatic, mucosal melanomaEuropean Journal of Cancer, 2013
- SF3B1 Mutations Are Associated with Alternative Splicing in Uveal MelanomaCancer Discovery, 2013
- Primary mucosal melanomas: a comprehensive review.2012
- KIT Pathway Alterations in Mucosal Melanomas of the Vulva and Other SitesClinical Cancer Research, 2011
- KIT amplification and gene mutations in acral/mucosal melanoma in KoreaAPMIS, 2011
- Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomasBritish Journal of Cancer, 2008
- NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression.2003
- Mutations of the BRAF gene in human cancerNature, 2002