title: Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables.
abstract: BACKGROUND
  Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes.
  
  
  METHODS
  In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n=41) as well as in tumors from BRCA2 (n=66) mutation carriers and in tumors from unselected cases of breast cancer (n =68).
  
  
  RESULTS
  The frequency of LOH in these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2-associated tumors and 8-33% in unselected tumors. LOH was significantly more frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological variables that were found significantly associated (p< or =0.05) with LOH at specific markers were: high percentage of cells in S-phase, negative estrogen receptor status, young age at diagnosis and large tumors. Deletion mapping indicates the existence of seven non-overlapping regions at chromosome 4, which were identified in all three groups of tumors. Three of these seven regions, 4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast cancer previously.
  
  
  CONCLUSIONS
  The results manifest the frequent alterations of chromosome 4 in BRCA1-associated breast tumors and indicate the location of several genes of potential importance in breast cancer development.
authors.affiliation: Department of Pathology, Landspitali-University Hospital by Hringbraut, Reykjavik, Iceland.
authors.forename: Hrefna K
authors.initials: HK
authors.lastname: Johannsdottir
authors.forename: Gudrun
authors.initials: G
authors.lastname: Johannesdottir
authors.forename: Bjarni A
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: Hannaleena
authors.initials: H
authors.lastname: Eerola
authors.forename: Adalgeir
authors.initials: A
authors.lastname: Arason
authors.forename: Oskar T H
authors.initials: OT
authors.lastname: Johannsson
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.forename: Valgardur
authors.initials: V
authors.lastname: Egilsson
authors.forename: Hakan
authors.initials: H
authors.lastname: Olsson
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Rosa B
authors.initials: RB
authors.lastname: Barkardottir
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D009693:Nucleic Acid Hybridization
chemical_list: D004273:DNA, Neoplasm