title: Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia.
abstract: In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer.
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK. Electronic address: christine.harrison@newcastle.ac.uk.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Schwab
mesh_terms: D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15; D002891:Chromosomes, Human, Pair 21; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012303:Ring Chromosomes; D012306:Risk; D014178:Translocation, Genetic
keywords: Centromeres; Leukaemia predisposition; iAMP21-ALL; rob(15;21)c