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Cutaneous carcinosarcoma: further insights into its mutational landscape through massive parallel genome sequencing

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Abstract

Cutaneous carcinosarcoma (CCS) is an extraordinarily rare neoplasm with a biphasic morphological pattern exhibiting both epithelial and sarcomatoid components. Although its histogenesis and biological aspects remain poorly understood, previous studies have postulated that this tumor may arise from single cancer stem cells which subsequently differentiate into distinct tumor lineages. In this study, we explored a wide array of mutational hot spot regions, through high-depth next-generation sequencing of 47 cancer-associated genes in order to assess the mutational landscape of these tumors and investigate whether the epithelial and mesenchymal components shared the same genetic signatures. Results from this study confirm that despite their striking phenotypic differences, both elements of this infrequent tumor indeed share a common clonal origin. Additionally, CCS appears to embrace a heterogeneous spectrum with specific underlying molecular signatures correlating with the defining epithelial morphotype, with those carcinosarcomas exhibiting a squamous cell carcinoma epithelial component exhibiting diverse point mutations and deletions in the TP53 gene, and those with a basal cell carcinoma morphotype revealing a more complex mutational landscape involving several genes. Also, the fact that our findings involve several targetable gene pathways suggests that the underlying molecular events driving the pathogenesis of CCS may represent future potential targets for personalized therapies.

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Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    Alberto Paniz-Mondolfi, A. Hafeez Diwan & Yve Huttenbach

  2. Departments of Biochemistry and Dermatopathology, Fundación Jacinto Convit (SAIB/IVSS) & Universidad de Los Andes (ULA), Caracas/Mérida, Venezuela

    Alberto Paniz-Mondolfi

  3. Molecular Diagnostics Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rajesh Singh, Bedia A. Barkoh, Ronald Cason, John Galbincea & Rajyalakshmi Luthra

  4. Department of Anatomic Pathology, University of Washington Medical Center, Seattle, WA, USA

    George Jour

  5. Department of Dermatopathology, Miraca Life Sciences Research Institute & Tufts University School of Medicine, Boston, MA, USA

    Mandana Mahmoodi

  6. Laboratorio de Señalización Celular y Bioquímica de Parásitos, Instituto de Estudios Avanzados (IDEA), Caracas, Venezuela

    Gustavo Benaim

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  1. Alberto Paniz-Mondolfi
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  2. Rajesh Singh
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Correspondence to Alberto Paniz-Mondolfi.

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Paniz-Mondolfi, A., Singh, R., Jour, G. et al. Cutaneous carcinosarcoma: further insights into its mutational landscape through massive parallel genome sequencing. Virchows Arch 465, 339–350 (2014). https://doi.org/10.1007/s00428-014-1628-0

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  • DOI: https://doi.org/10.1007/s00428-014-1628-0

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