title: Complex chromosomal abnormalities in utero, 5 years before leukaemia.
abstract: Prenatal acquisition of leukaemia-associated gene rearrangements is a well-established phenomenon. This is the first report of a complex cytogenetic clone, in association with an ETV6/AML1 fusion, developing in utero. Identical twin girls, aged 4 years, developed ETV6/AML1-positive acute lymphoblastic leukaemia (ALL) within 3 months of one another. Both demonstrated an identical four way, variant t(12;21). There was gain of an AML1 signal in twin 1 and loss of an ETV6 one in twin 2 at interphase. This unique case study demonstrates that ETV6/AML1 fusion and the associated complex chromosomal rearrangements occurred in utero. Clonal expansion of the abnormal cell in one twin was followed by metastasis to the other. There was a prolonged preleukaemic phase, which lasted well into childhood. The short time between the two diagnoses of ALL suggests a common precipitating event. The significance of the different secondary markers remains unclear.
authors.affiliation: Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK. zjb@soton.ac.uk
authors.forename: Zoë J
authors.initials: ZJ
authors.lastname: Broadfield
authors.forename: Richard D W
authors.initials: RD
authors.lastname: Hain
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: G
authors.initials: G
authors.lastname: Reza Jalali
authors.forename: Mark
authors.initials: M
authors.lastname: McKinley
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalová
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Robinson
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanová
authors.forename: Mary
authors.initials: M
authors.lastname: Martineau
mesh_terms: D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D002999:Clone Cells; D050676:Core Binding Factor Alpha 2 Subunit; D004200:Diseases in Twins / Q000196:embryology* / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000196:embryology* / Q000235:genetics*; D011289:Preleukemia / Q000196:embryology / Q000235:genetics; D014178:Translocation, Genetic; D014430:Twins, Monozygotic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein