The mutational repertoire of uterine sarcomas and carcinosarcomas in a Brazilian cohort: A preliminary study

Leonardo Tomiatti da Costa, Laura Gonzalez Dos Anjos, Luciane Tsukamoto Kagohara, Giovana Tardin Torrezan, Claudia A.Andrade De Paula, Edmund Chada Baracat, Dirce Maria Carraro, Katia Candido Carvalho

Research output: Contribution to journalArticlepeer-review


OBJECTIVES: The present study aimed to contribute to the catalog of genetic mutations involved in the carcinogenic processes of uterine sarcomas (USs) and carcinosarcomas (UCSs), which may assist in the accurate diagnosis of, and selection of treatment regimens for, these conditions. METHODS: We performed gene-targeted next-generation sequencing (NGS) of 409 cancer-related genes in 15 US (7 uterine leiomyosarcoma [ULMS], 7 endometrial stromal sarcoma [ESS], 1 adenosarcoma [ADS]), 5 UCS, and 3 uterine leiomyoma (ULM) samples. Quality, frequency, and functional filters were applied to select putative somatic variants. RESULTS: Among the 23 samples evaluated in this study, 42 loss-of-function (LOF) mutations and 111 missense mutations were detected, with a total of 153 mutations. Among them, 66 mutations were observed in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. TP53 (48%), ATM (22%), and PIK3CA (17%) were the most frequently mutated genes. With respect to specific tumor subtypes, ESS showed mutations in the PDE4DIP, IGTA10, and DST genes, UCS exhibited mutations in ERBB4, and ULMS showed exclusive alterations in NOTCH2 and HER2. Mutations in the KMT2A gene were observed exclusively in ULM and ULMS. In silico pathway analyses demonstrated that many genes mutated in ULMS and ESS have functions associated with the cellular response to hypoxia and cellular response to peptide hormone stimulus. In UCS and ADS, genes with most alterations have functions associated with phosphatidylinositol kinase activity and glycerophospholipid metabolic process. CONCLUSION: This preliminary study observed pathogenic mutations in US and UCS samples. Further studies with a larger cohort and functional analyses will foster the development of a precision medicine-based approach for the treatment of US and UCS.

Original languageEnglish (US)
Article numbere2324
Pages (from-to)1-15
Number of pages15
StatePublished - 2021


  • Carcinosarcoma
  • DNA Sequence Analysis
  • Mutation
  • Sarcoma

ASJC Scopus subject areas

  • Medicine(all)


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