Identification of an Actionable Mutation of KIT in a Case of Extraskeletal Myxoid Chondrosarcoma

Milena Urbini, Valentina Indio, Annalisa Astolfi, Giuseppe Tarantino, Salvatore Lorenzo Renne, Silvana Pilotti, Angelo Paolo Dei Tos, Roberta Maestro, Paola Collini, Margherita Nannini, Maristella Saponara, Ludovica Murrone, Gian Paolo Dagrada, Chiara Colombo, Alessandro Gronchi, Andrea Pession, Paolo Giovanni Casali, Silvia Stacchiotti, Maria Abbondanza Pantaleo

Research output: Contribution to journalArticlepeer-review


Extraskeletal myxoid chondrosarcoma (EMC) is an extremely rare soft tissue sarcoma, marked by a translocation involving the NR4A3 gene. EMC is usually indolent and moderately sensitive to anthracycline-based chemotherapy. Recently, we reported on the therapeutic activity of sunitinib in a series of EMC cases, however the molecular target of sunitinib in EMC is unknown. Moreover, there is still the need to identify alternative therapeutic strategies. To better characterize this disease, we performed whole transcriptome sequencing in five EMC cases. Peculiarly, in one sample, an in-frame deletion (c.1735_1737delGAT p.D579del) was identified in exon 11 of KIT. The deletion was somatic and heterozygous and was validated both at DNA and mRNA level. This sample showed a marked high expression of KIT at the mRNA level and a mild phosphorylation of the receptor. Sanger sequencing of KIT in additional 15 Formalin Fixed Paraffin Embedded (FFPE) EMC did not show any other mutated cases. In conclusion, exon 11 KIT mutation was detected only in one out of 20 EMC cases analyzed, indicating that KIT alteration is not a recurrent event in these tumors and cannot explain the EMC sensitivity to sunitinib, although it is an actionable mutation in the individual case in which it has been identified.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Issue number7
Publication statusPublished - Jun 23 2018


  • Base Sequence
  • Chondrosarcoma/diagnosis
  • Computational Biology
  • DNA-Binding Proteins/genetics
  • Exons
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms, Connective and Soft Tissue/diagnosis
  • Oncogene Proteins, Fusion/genetics
  • Proto-Oncogene Proteins c-kit/genetics
  • RNA-Binding Protein EWS/genetics
  • Receptors, Steroid/genetics
  • Receptors, Thyroid Hormone/genetics
  • Sequence Deletion
  • Transcriptome
  • Whole Exome Sequencing


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