title: Deletions of chromosome 5q13.3 and 17p loci cooperate in myeloid neoplasms.
abstract: Nonrandom interstitial deletions and monosomy of chromosomes 5, 7, and 17 in refractory myelodysplasia (MDS) and acute myelogenous leukemia (AML) suggest a multistep pathway that culminates in aggressive clinical course. Because cytogenetic studies frequently identify chromosome 5 and 17 deletions within a single clone, we searched for allele loss for 5q loci and TP53 gene mutations in the same leukemic samples. Cosegregating deletions of chromosomes 5 and 17 were found to specifically include the 5q13.3 interval between the loci D5S672 and D5S620/D5S626, a locus hypothesized to harbor a tumor suppressor gene(1) and the TP53 gene on 17p. A rare patient with secondary refractory MDS and an unbalanced translocation [der(5;17)], which resulted in deletions of the 5q13.3-qter and 17p loci, provided clues on the sequence of genetic alterations. Serial molecular analysis of this patient revealed a dysplastic clone with der(5;17), which gave rise to a leukemic clone on acquiring an inactivating mutation of TP53. Our findings are consistent with functional cooperation between a putative tumor suppressor gene at 5q13.3 that contributes toward the progression of early stages of MDS, and the TP53 gene when mutated, causes transformation to AML. (Blood. 2000;95:2138-2143)
authors.affiliation: Department of Molecular Genetics, Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Castro
authors.forename: J C
authors.initials: JC
authors.lastname: Liang
authors.forename: L
authors.initials: L
authors.lastname: Nagarajan
mesh_terms: D000483:Alleles; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics; D002872:Chromosome Deletion; D018244:Chromosomes, Artificial, Yeast; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D020451:Contig Mapping; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020161:Physical Chromosome Mapping; D014407:Tumor Cells, Cultured