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Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations

Author:
  • M Tirkkonen
  • O Johannsson
  • B A Agnarsson
  • Håkan Olsson
  • S Ingvarsson
  • R Karhu
  • M Tanner
  • J Isola
  • R B Barkardottir
  • Åke Borg
  • O P Kallioniemi
Publishing year: 1997-04-01
Language: English
Pages: 7-1222
Publication/Series: Cancer Research
Volume: 57
Issue: 7
Document type: Journal article
Publisher: American Association for Cancer Research Inc.

Abstract english

BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers from 21 BRCA1 mutation carriers, 15 BRCA2 mutation carriers, and 55 unselected controls. The total number of genetic changes was almost two times higher in tumors from both BRCA1 and BRCA2 mutation carriers than in the control group. In BRCA1 tumors, losses of 5q (86%), 4q (81%), 4p (64%), 2q (40%), and 12q (40%) were significantly more common than in the control group (7-13%). BRCA2 tumors were characterized by a higher frequency of 13q (73%) and 6q (60%) losses and gains of 17q22-q24 (87%) and 20q13 (60%) as compared to the prevalence of these changes in the control group (12-18%). In conclusion, accumulation of somatic genetic changes during tumor progression may follow a unique pathway in individuals genetically predisposed to cancer, especially by the BRCA1 gene. Activation or loss of genes in the affected chromosomal regions may be selected for during tumor progression in cells lacking functional BRCA1 or BRCA2. Identification of such genes could provide targets for therapeutic intervention and early diagnosis.

Keywords

  • Cancer and Oncology
  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA2 Protein
  • Breast Neoplasms
  • Carcinoma, Ductal, Breast
  • Chromosome Deletion
  • Chromosomes, Human, Pair 4
  • Chromosomes, Human, Pair 5
  • Disease Progression
  • Female
  • Genes, BRCA1
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Middle Aged
  • Neoplasm Proteins
  • Nucleic Acid Hybridization
  • Polymorphism, Single-Stranded Conformational
  • Transcription Factors

Other

Published
  • Lund Melanoma Study Group
  • Familial Breast Cancer
  • ISSN: 0008-5472
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90