Virchows Archiv

, Volume 465, Issue 3, pp 339–350

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

  • Alberto Paniz-Mondolfi
  • Rajesh Singh
  • George Jour
  • Mandana Mahmoodi
  • A. Hafeez Diwan
  • Bedia A. Barkoh
  • Ronald Cason
  • Yve Huttenbach
  • Gustavo Benaim
  • John Galbincea
  • Rajyalakshmi Luthra
Original Article

DOI: 10.1007/s00428-014-1628-0

Cite this article as:
Paniz-Mondolfi, A., Singh, R., Jour, G. et al. Virchows Arch (2014) 465: 339. doi:10.1007/s00428-014-1628-0

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.

Keywords

CarcinosarcomaCutaneousMutationsNext-generation sequencingStem cellsHistogenesis

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Alberto Paniz-Mondolfi
    • 1
    • 2
  • Rajesh Singh
    • 3
  • George Jour
    • 4
  • Mandana Mahmoodi
    • 5
  • A. Hafeez Diwan
    • 1
  • Bedia A. Barkoh
    • 3
  • Ronald Cason
    • 3
  • Yve Huttenbach
    • 1
  • Gustavo Benaim
    • 6
  • John Galbincea
    • 3
  • Rajyalakshmi Luthra
    • 3
  1. 1.Department of Pathology and ImmunologyBaylor College of MedicineHoustonUSA
  2. 2.Departments of Biochemistry and DermatopathologyFundación Jacinto Convit (SAIB/IVSS) & Universidad de Los Andes (ULA)Caracas/MéridaVenezuela
  3. 3.Molecular Diagnostics LaboratoryThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Anatomic PathologyUniversity of Washington Medical CenterSeattleUSA
  5. 5.Department of DermatopathologyMiraca Life Sciences Research Institute & Tufts University School of MedicineBostonUSA
  6. 6.Laboratorio de Señalización Celular y Bioquímica de ParásitosInstituto de Estudios Avanzados (IDEA)CaracasVenezuela