Genetic analyses of a secondary poroma and trichoblastoma in a HRAS-mutated sebaceous nevus.
NOTCH2
TP53
HRAS gene
poroma
sebaceous nevus of Jadassohn
Journal
The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
revised:
01
04
2021
received:
28
01
2021
accepted:
03
04
2021
pubmed:
29
4
2021
medline:
4
8
2021
entrez:
28
4
2021
Statut:
ppublish
Résumé
A sebaceous nevus is a congenital skin hamartoma caused by postzygotic HRAS or KRAS mosaic mutations. With age, affected individuals may develop secondary tumors within a sebaceous nevus. RAS mutations are harbored from the onset of sebaceous nevus, and further mutations can be expected to be required in order to explain the initiation of secondary tumors. However, genetic analyses of the secondary tumors have not been conducted. Herein, we describe the rare coexistence of a poroma and a trichoblastoma arising in a sebaceous nevus. This is the first report of an investigation of multiple genes in a secondary tumor in an SN. First, HRAS c.37G>C, which is the common mutation in sebaceous nevus, was detected in all three lesions (sebaceous nevus, poroma, and trichoblastoma). Next, to elucidate the potential second-hit mutations in the secondary poroma and trichoblastoma, we applied a panel sequencing for skin cancers that was newly developed in our institution. Our comparison of the mutational profile of 95 skin cancer-related genes in each of the three lesions newly revealed TP53 p.R158P in the poroma and NOTCH2 p.G329S in the trichoblastoma. TP53 p.R158P has been determined as a pathogenic mutation in other tumors, and NOTCH2 p.G329S was a novel mutation. We identified two novel mutations that may have contributed to the pathogenesis of the secondary tumor's development. The roles of the mutations remain unclear.
Identifiants
pubmed: 33908086
doi: 10.1111/1346-8138.15919
doi:
Substances chimiques
HRAS protein, human
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1268-1272Subventions
Organisme : Japan Society for the Promotion of Science
ID : 16H06279
Informations de copyright
© 2021 Japanese Dermatological Association.
Références
Groesser L, Herschberger E, Ruetten A, Ruivenkamp C, Lopriore E, Zutt M, et al. Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome. Nat Genet. 2012;44:783-7.
Harms PW, Hovelson DH, Cani AK, Omata K, Haller MJ, Wang ML, et al. Porocarcinomas harbor recurrent HRAS-activating mutations and tumor suppressor inactivating mutations. Hum Pathol. 2016;51:25-31.
Shen A-S, Peterhof E, Kind P, Rütten A, Zelger B, Landthaler M, et al. Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum. Hum Pathol. 2015;46:272-6.
Idriss MH, Elston DM. Secondary neoplasms associated with nevus sebaceus of Jadassohn: a study of 707 cases. J Am Acad Dermatol. 2014;70:332-7.
Kawakami Y, Hafner C, Oyama N, Yamamoto T. A case of sebaceous naevus of the leg with secondarily developed trichoblastoma. Acta Derm Venereol. 2010;90:194-5.
Wang E, Lee JS, Kazakov DV. A rare combination of sebaceoma with carcinomatous change (sebaceous carcinoma), trichoblastoma, and poroma arising from a nevus sebaceus. J Cutan Pathol. 2013;40:676-82.
Bosic M, Kirchner M, Brasanac D, Leichsenring J, Lier A, Volckmar A-L, et al. Targeted molecular profiling reveals genetic heterogeneity of poromas and porocarcinomas. Pathology. 2018;50:327-32.
Ichihashi N, Kitajima Y. Loss of heterozygosity of adenomatous polyposis coli gene in cutaneous tumors as determined by using polymerase chain reaction and paraffin section preparations. J Dermatol Sci. 2000;22:102-6.
Sekine S, Kiyono T, Ryo E, Ogawa R, Wakai S, Ichikawa H, et al. Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma. J Clin Invest. 2019;129:3827-32.
Kazakov DV, Sima R, Vanecek T, Kutzner H. Mutations in exon 3 of the CTNNB1 gene (beta-catenin gene) in cutaneous adnexal tumors. Am J Dermatopathol. 2009;31:248-55.
Kazakov DV, Schaller J, Vanecek T, Kacerovska D, Michal M. Brooke-Spiegler syndrome: report of a case with a novel mutation in the CYLD gene and different types of somatic mutations in benign and malignant tumors. J Cutan Pathol. 2010;37:886-90.
Akalin T, Sen S, Yücetürk A, Kandiloğlu G. P53 protein expression in eccrine poroma and porocarcinoma. Am J Dermatopathol. 2001;23:402-6.
Brachmann RK, Vidal M, Boeke JD. Dominant-negative p53 mutations selected in yeast hit cancer hot spots. Proc Natl Acad Sci USA. 1996;93:4091-5.
Barta JA, Pauley K, Kossenkov AV, McMahon SB. The lung-enriched p53 mutants V157F and R158L/P regulate a gain of function transcriptome in lung cancer. Carcinogenesis. 2020;41:67-77.
Aubin-Houzelstein G. Notch signaling and the developing hair follicle. Adv Exp Med Biol. 2012;727:142-60.