Details

Autor(en) / Beteiligte

• de Silva, Michelle G
• Kantharidis, Phillip
• Scherer, Stephen W
• Rayeroux, Kathleen
• Campbell, Lynda
• Tsui, Lap-Chee
• Zalcberg, John R

Titel

Physical Mapping of a Tandem Duplication on the Long Arm of Chromosome 7 Associated with a Multidrug Resistant Phenotype

Ist Teil von

• Cancer genetics and cytogenetics, 1999-04, Vol.110 (1), p.28-33

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

1999

Link zum Volltext

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• 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.