title: A variant c-KIT mutation, D816H, fundamental to the sequential development of an ovarian mixed germ cell tumor and systemic mastocytosis with chronic myelomonocytic leukemia.
abstract: An activating point mutation of the c-KIT tyrosine kinase receptor gene, D816H, has been described in germ cell tumors (GCTs). We report an adolescent diagnosed with an ovarian mixed GCT and systemic mastocytosis with chronic myelomonocytic leukemia (SM-CMML). The teratoma and dysgerminoma differed by copy number aberrations via single nucleotide polymorphism (SNP) microarray, but were inclusive of the same c-KIT D816H point mutation (c.2446G>C) also identified in blood and bone marrow mast cells. These findings indicate not only a clonal origin of the GCT and hematologic malignancy, but also suggest a rare KIT mutation may be playing a fundamental role in malignancy development.
authors: Department of Pediatric Hematology/Oncology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors: Sarah G
authors: SG
authors: Mitchell
authors: Department of Pathology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors: Silvia T
authors: ST
authors: Bunting
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors: Debra
authors: D
authors: Saxe
authors: Department of Pediatric Hematology/Oncology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors: Thomas
authors: T
authors: Olson
authors: Department of Pediatric Hematology/Oncology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors: Frank G
authors: FG
authors: Keller
mesh_terms: D000293:Adolescent; D005260:Female; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009373:Neoplasms, Germ Cell and Embryonal / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: c-KIT D816H mutation; chronic myelomonocytic leukemia; germ cell tumor; isochromosome 12p; systemic mastocytosis