RESUMEN
Abstract BACKGROUND: Kaposiform hemangioendothelioma is a rare, intermediate, malignant tumor. The tumor's etiology remains unknown and there are no specific treatments. OBJECTIVE: In this study, we performed exome sequencing using DNA from a Kaposiform hemangioendothelioma patient, and found putative candidates for the responsible mutations. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
Asunto(s)
Humanos , Masculino , Preescolar , Mutación Missense , Síndrome de Kasabach-Merritt/genética , Síndrome de Kasabach-Merritt/patología , Exoma , Hemangioendotelioma/genética , Hemangioendotelioma/patología , Valores de Referencia , Análisis Mutacional de ADN , Imagen por Resonancia Magnética , Genes p53/genética , Genes APC , Tejido Subcutáneo/patología , Estudios de Asociación Genética , Frecuencia de los GenesRESUMEN
BACKGROUND:: Kaposiform hemangioendothelioma is a rare, intermediate, malignant tumor. The tumor's etiology remains unknown and there are no specific treatments. OBJECTIVE:: In this study, we performed exome sequencing using DNA from a Kaposiform hemangioendothelioma patient, and found putative candidates for the responsible mutations. METHOD:: 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. RESULTS:: 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. CONCLUSION:: 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.
Asunto(s)
Exoma , Hemangioendotelioma/genética , Hemangioendotelioma/patología , Síndrome de Kasabach-Merritt/genética , Síndrome de Kasabach-Merritt/patología , Mutación Missense , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/patología , Preescolar , Análisis Mutacional de ADN , Frecuencia de los Genes , Genes APC , Genes p53/genética , Estudios de Asociación Genética , Humanos , Imagen por Resonancia Magnética , Masculino , Valores de Referencia , Tejido Subcutáneo/patologíaRESUMEN
A 13-year old girl was diagnosed as having a bone hemangioendothelioma. Cytogenetic studies identified the presence of a small supernumerary marker chromosome in this patient. Classical cytogenetic methods using G-, C-, Ag-NOR-banding were supplemented by spectral karyotyping (SKY) and fluorescence in situ hybridization to reveal a karyotype 47,XX,+mar.ish der(22)(D22S543+) karyotype in cells derived from the tumor and lymphocytes. These findings suggest that the supernumerary marker chromosome originated from the proximal centromeric region of chromosome 22, and that trisomy of the region 22q11 was not associated with adverse phenotypic effects, but that the presence of trisomy 22q11 may be related to the development of this tumor.