title: KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication.
abstract: OBJECTIVE
  Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia.
  
  
  METHODS
  In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations.
  
  
  RESULTS
  Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1%) adult CBFL cases and 6 of the 49 (12.2%) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele.
  
  
  CONCLUSIONS
  These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.
authors.affiliation: Department of Biology and Genetics for Medical Sciences, Medical Faculty, University of Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Beghini
authors.forename: Carla B
authors.initials: CB
authors.lastname: Ripamonti
authors.forename: Roberto
authors.initials: R
authors.lastname: Cairoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Patrizia
authors.initials: P
authors.lastname: Colapietro
authors.forename: Francesca
authors.initials: F
authors.lastname: Elice
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Nadali
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grillo
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
mesh_terms: D000328:Adult; D002648:Child; D050660:Core Binding Factors / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis; D020440:Gene Duplication; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D050660:Core Binding Factors; D019009:Proto-Oncogene Proteins c-kit