A genomic survey of sarcomas on sun-exposed skin reveals distinctive candidate drivers and potentially targetable mutations.
Hum Pathol
; 102: 60-69, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32540221
ABSTRACT
Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping microscopic and immunophenotypic features. Improved understanding of molecular alterations in these tumors may provide diagnostic and therapeutic insights. We characterized 111 cutaneous sarcomatoid malignancies and their counterparts, including primary cutaneous angiosarcoma (n = 7), atypical fibroxanthoma (AFX) (n = 21), pleomorphic dermal sarcoma (PDS) (n = 17), extracutaneous undifferentiated pleomorphic sarcoma (n = 8), cutaneous leiomyosarcoma (LMS) (n = 5), extracutaneous LMS (n = 9), sarcomatoid squamous cell carcinoma (spindle cell squamous cell carcinoma) (S-SCC) (n = 24), and conventional cutaneous squamous cell carcinoma (SCC) (n = 20), by next-generation sequencing (NGS) using the StrataNGS panel for copy number variations, mutations, and/or fusions in more than 60 cancer-related genes. TP53 mutations were highly recurrent in most groups. Angiosarcoma displayed previously reported MYC amplifications, as well as CCND1 gains. RB1 mutations were relatively restricted to cutaneous LMS. As previously reported, PIK3CA mutations occurred in AFX, whereas RAS activation was more frequent in PDS. CDKN2A mutations were recurrent in AFX and S-SCC, whereas PDS displayed frequent CDKN2A deletion. S-SCC displayed mutational similarity to conventional SCC. BRCA1/2 mutations were specific to tumors with disease progression. In a subset, we detected potential driver events novel to these tumor types activating mutations in IDH2 (PDS), MAP2K1 (angiosarcoma, PDS), and JAK1 (S-SCC) and copy gains in FGFR1 (angiosarcoma, S-SCC), KIT (AFX), MET (PDS), and PDGFRA (PDS). Our findings confirm and expand the spectrum of known genomic aberrations, including potential targetable drivers, in cutaneous sarcomatoid malignancies. In addition, certain events are relatively specific to particular tumors within this differential diagnosis and hence might be diagnostically informative.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
/
Neoplasias Cutâneas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA