Genetic analyses of a secondary poroma and trichoblastoma in a HRAS‐mutated sebaceous nevus

Abstract

Poroma and trichoblastoma are rare adnexal skin neoplasms that occur sporadically or secondary to a sebaceous nevus (SN).Postzygotic mosaic mutations in HRAS and KRAS genes cause SN, 1 and these RAS-activating mutations have been detected in tumors including sporadic poroma and trichoblastoma. 2,3 Sebaceous nevi are congenital, and the risk of secondary tumors increases with age, suggesting that additional gene mutations may contribute to the tumorigenesis. The genetic landscape of the secondary tumors is still largely unexplored. Herein, we describe the case of a patient with a secondary poroma and a trichoblastoma arising in an SN with an HRAS p.G13R mutation. We investigated additional gene aberrations of the poroma and trichoblastoma in the SN with panel sequencing that was developed for skin cancers.

Whole‐exome sequencing of secondary tumors arising from nevus sebaceous revealed additional genomic alterations besides RAS mutations

“…In our study, known hotspot RAS mutations of NS were consistently found in six tumors ( HRAS p.G13R) as well as in six NS lesions ( HRAS p.G13R, and KRAS p.G12C or p.G12D) 4–7 . This finding indicates that secondary tumor would be developed from RAS mutated cells in NS, which was consistent with previous studies 6–9 . Interestingly, we also identified a tumor with HRAS p.Q61R mutation.…”

“…[4][5][6][7] This finding indicates that secondary tumor would be developed from RAS mutated cells in NS, which was consistent with previous studies. [6][7][8][9] Interestingly, we also identified a tumor with HRAS p.Q61R mutation. This mutation is another known hotspot of HRAS which was rarely reported in case of NS with cutaneous-skeletal hypophosphatemia syndrome.…”

“…[4][5][6][7] Secondary tumors arising from NS also harbor the same RAS mutations in a few cases. [6][7][8][9] However, additional genomic alterations, underlying tumorigenesis in NS lesions have not been clarified. To investigate genomic alterations in secondary tumors arising from NS, we analyzed somatic mutations and copy number alterations (CNAs) of eight secondary tumors arising from NS as well as eight NS lesions without secondary tumors using whole-exome sequencing (WES).…”

“…NS is a mosaic RASopathy with postzygotic HRAS (p.G13R) or KRAS (p.G12D) hotspot mutations 4–7 . Secondary tumors arising from NS also harbor the same RAS mutations in a few cases 6–9 . However, additional genomic alterations, underlying tumorigenesis in NS lesions have not been clarified.…”

A Case of Apocrine Carcinoma Arising in a Sebaceous Naevus: Detection of HRAS G13R Mutation

“…DNA sequencing and immunohistochemical staining are available to detect this mutation. Many secondary tumours also have the same mutations as the original lesions ( 1 , 4 , 5 ). However, in the 3 cases of sporadic AC that we examined (Table SI), no mutations in exon 2 of HRAS (Fig.…”