Physical mapping of a tandem duplication on the long arm of chromosome 7 associated with a multidrug resistant phenotype.
Both the expression of the multidrug transporter, P-glycoprotein (Pgp), and abnormalities of the long arm of chromosome 7 have been shown to be adverse prognostic indicators in acute leukemias. In this study, a clonal duplication, dup(7)(q11.1q31.1), inherited with the classical multidrug resistant phenotype in a drug-resistant derivative of a human T-cell leukemia cell line was characterized. The position of the duplication was of interest as the gene which encodes Pgp, MDR1, is located on the long arm of chromosome 7 at position 7q21.1. Fluorescence in situ hybridization (FISH) analysis with a chromosome 7-specific painting probe confirmed the composition of the abnormal chromosome. A YAC clone hybridizing to the MDR1 locus confirmed that this gene was located within the duplicated region of the derivative chromosome. With a panel of well-characterized YAC clones, the duplicated segment was found to be a direct tandem duplication, somewhat larger than estimated by conventional cytogenetics. The proximal and distal breakpoints of the abnormality were located and a YAC clone spanning the distal breakpoint was identified. This clone is of particular interest, as it harbors the markers D7S523 and D7S471, close to which a putative tumor suppressor gene is thought to lie. Further examination of the breakpoint region may therefore illuminate the mechanism of Pgp upregulation as well as providing information about a tumor suppressor gene.
de Silva
M G
MG
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia.
Kantharidis
P
P
Scherer
S W
SW
Rayeroux
K
K
Campbell
L
L
Tsui
L C
LC
Zalcberg
J R
JR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D020161:Physical Chromosome Mapping; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1