title: Loss of TP53 is due to rearrangements involving chromosome region 17p10 approximately p12 in chronic lymphocytic leukemia.
abstract: Loss of tumor protein 53 (TP53) has been associated with aggressive disease and poor response to therapy in B-cell chronic lymphocytic leukemia (B-CLL). TP53 is located at chromosome band 17p13 and its absence can be detected by fluorescence in situ hybridization (FISH) in the interphase nuclei of 8-10% patients with B-CLL. To study the cytogenetic mechanism for loss of TP53, metaphase and interphase FISH studies were conducted on 16 B-CLL patients to investigate 17p10 to 17p12, a chromosome region known to be rich in low-copy DNA repeats. Loss of TP53 was caused by an isochromosome with breakpoints between 17p10 and 17p11.2 in four patients, an unbalanced translocation involving 17p10 to 17p11.2 in nine patients, and an unbalanced translocation involving 17p11.2 to 17p12 in three patients. These findings indicate that loss of TP53 results from the absence of nearly the entire chromosome 17 p-arm rather than to monosomy 17 or deletions of TP53. Translocations or isochromosome formations at sites of low-copy DNA repeats in 17p10 to 17p12 appear to be the mechanism for the loss of TP53 in B-CLL.
authors.affiliation: Cytogenetics Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Fink
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smoley
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Stockero
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Paternoster
authors.forename: Erik C
authors.initials: EC
authors.lastname: Thorland
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Van Dyke
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
mesh_terms: D000368:Aged; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018404:Isochromosomes; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic