Deletions of chromosome 5q13.3 and 17p loci cooperate in myeloid neoplasms.
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)
Castro
P D
PD
Department of Molecular Genetics, Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Liang
J C
JC
Nagarajan
L
L
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