title: Frequent somatic deletion of the 13q12.3 locus encompassing BRCA2 in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) has consistent 13q chromosomal abnormalities detected by conventional cytogenetics. Using interphase cytogenetics we show deletion of a 1-megabase 13q12.3 locus, encompassing the BRCA2 gene, in 80% of 35 CLL cases studied. Homozygous deletion of BRCA2, located within the minimal deletion consensus, was detected in a significant population of cells in 60% of the cases. Deletion of the previously described 13q14 locus (analyzed with RB1 and D13S25 probes) was seen in 63% of the cases. Homozygous deletion of RB1 was seen in one case. Seven of the cases (32%) with D13S25 deletion had a population of cells with homozygous deletion. Deletions at the 13q12 and 13q14 loci result from distinct events because they were not contiguous. These data provide evidence for the existence of a new tumor suppressor locus in B-cell CLL located at 13q12.3. BRCA2, located within the minimal deletion consensus, is a candidate for the gene whose somatic inactivation could play a role in the initiation and or progression of B-cell CLL.
authors.affiliation: Academic Department of Haematology and Cytogenetics, Royal Marsden Hospital, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Garcia-Marco
authors.forename: C
authors.initials: C
authors.lastname: Caldas
authors.forename: C M
authors.initials: CM
authors.lastname: Price
authors.forename: L M
authors.initials: LM
authors.lastname: Wiedemann
authors.forename: A
authors.initials: A
authors.lastname: Ashworth
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000483:Alleles; D024682:BRCA2 Protein; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics* / Q000648:ultrastructure; D002999:Clone Cells / Q000473:pathology; D016384:Consensus Sequence; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics*; D011446:Prospective Studies; D016160:Retinoblastoma Protein / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors