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Intrachromosomal amplification of chromosome 21 (iAMP21) may arise from a breakage–fusion–bridge cycle
Author(s) -
Robinson Hazel M.,
Harrison Christine J.,
Moorman Anthony V.,
Chudoba Ilse,
Strefford Jonathan C.
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20412
Subject(s) - biology , fluorescence in situ hybridization , chromosome 21 , amplicon , karyotype , genetics , metaphase , gene duplication , locus (genetics) , dup , chromosome , chromosomal translocation , fusion gene , breakpoint , chromosome 22 , microbiology and biotechnology , gene , polymerase chain reaction
Intrachromosomal amplification of chromosome 21 (iAMP21), involving amplification of the RUNX1 gene and duplication of chromosome 21, dup(21q), defines a new cytogenetic subgroup in B‐lineage acute lymphoblastic leukemia (ALL) with a poor prognosis. Characterization of this abnormality has become vital to ensure that the most accurate detection method is used. We have previously defined common regions of amplification and deletion of chromosome 21 in these patients, although the level and extent of amplification within the amplicon was highly variable. This study, using interphase fluorescence in situ hybridization (FISH) with chromosome 21 locus specific probes, substantiated these findings in a large series of patients and confirmed that the amplicon always included RUNX1 . Thus, FISH with probes directed to the RUNX1 gene remains the most reliable detection method. Metaphase FISH, supported by G‐ and multiple color chromosomal banding (mBAND) revealed the patient specific morphology and genetic profile of the dup(21q) chromosomes, as well as the complexity of the intrachromosomal changes giving rise to them. These findings suggested that iAMP21 had arisen from a breakage–fusion–bridge cycle: a mechanism previously described in tumors, which we report for the first time in ALL. © 2007 Wiley‐Liss, Inc.