Exome sequence analysis of Kaposiform hemangioendothelioma: identification of putative driver mutations

• Published in: Anais brasileiros de dermatología 2016-11, Vol.91 (6), p.748-753
• Main Authors: Egashira, Sho, Jinnin, Masatoshi, Harada, Miho, Masuguchi, Shinichi, Fukushima, Satoshi, Ihn, Hironobu
• Format: Article
• Language: English
• Subjects: Child, Preschool; DERMATOLOGY; DNA Mutational Analysis; Exome; Gene Frequency; Genes, APC; Genes, p53 - genetics; Genetic Association Studies; Hemangioendothelioma; Hemangioendothelioma - genetics; Hemangioendothelioma - pathology; Humans; Investigation; Kasabach-Merritt Syndrome - genetics; Kasabach-Merritt Syndrome - pathology; Magnetic Resonance Imaging; Male; Mutation; Mutation, Missense; Reference Values; Sarcoma, Kaposi - genetics; Sarcoma, Kaposi - pathology; Subcutaneous Tissue - pathology
• ISSN: 0365-0596; 1806-4841; 1806-4841; 0365-0596
• DOI: 10.1590/abd1806-4841.20165026

Kaposiform hemangioendothelioma is a rare, intermediate, malignant tumor. The tumor's etiology remains unknown and there are no specific treatments. In this study, we performed exome sequencing using DNA from a Kaposiform hemangioendothelioma patient, and found putative candidates for the responsible mutations. The genomic DNA for exome sequencing was obtained from the tumor tissue and matched normal tissue from the same individual. Exome sequencing was performed on HiSeq2000 sequencer platform. Among oncogenes, germline missense single nucleotide variants were observed in the TP53 and APC genes in both the tumor and normal tissue. As tumor-specific somatic mutations, we identified 81 candidate genes, including 4 nonsense changes, 68 missense changes and 9 insertions/deletions. The mutations in ITGB2, IL-32 and DIDO1 were included in them. This is a pilot study, and future analysis with more patients is needed to clarify: the detailed pathogenesis of this tumor, the novel diagnostic methods by detecting specific mutations, and the new therapeutic strategies targeting the mutation.