Physical mapping of a tandem duplication on the long arm of chromosome 7 associated with a multidrug resistant phenotype

Michelle G. De Silva, Phillip Kantharidis, Stephen W. Scherer, Kathleen Rayeroux, Lynda Campbell, Lap Chee Tsui, John R. Zalcberg

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)28-33
Number of pages6
JournalCancer Genetics and Cytogenetics
Volume110
Issue number1
DOIs
Publication statusPublished - 1 Apr 1999
Externally publishedYes

Cite this