Mapping loss of heterozygosity in normal human breast cells from BRCA1 2 carriers

We have studied loss of heterozygosity at the BRCA1 and BRCA2 loci in 992 normal cell clones derived from topographically defined areas of normal tissue in four samples from BRCA1/BRCA2 mutation carriers. The frequency of loss of heterozygosity in the clones was low (1.01%), but it was found in all...

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Bibliographic Details
Published in:British journal of cancer 2006-08, Vol.95 (4), p.515-519
Main Authors: Clarke, C L, Sandle, J, Jones, A A, Sofronis, A, Patani, N R, Lakhani, S R
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Breast - cytology
Breast cancer
Breast Neoplasms - genetics
Cancer Research
Clone Cells
Drug Resistance
Epidemiology
Female
Gene Frequency
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Humans
Hyperplasia
Loss of Heterozygosity
Mastectomy
Medical research
Molecular Diagnostics
Molecular Medicine
Mutation
Oncology
Tumors
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Summary:We have studied loss of heterozygosity at the BRCA1 and BRCA2 loci in 992 normal cell clones derived from topographically defined areas of normal tissue in four samples from BRCA1/BRCA2 mutation carriers. The frequency of loss of heterozygosity in the clones was low (1.01%), but it was found in all four samples, whether or not a tumour was present. Topographical mapping revealed that the genetic changes were clustered in some breast samples. Our study confirms the previous finding that a field of genetic instability can exist around a tumour, suggesting that sufficient tissue must be removed at surgery to avoid local recurrence. We also demonstrate that such a field of genetic change can exist in morphologically normal tissue before a tumour develops and, for the first time, we demonstrate that the field is of a size greater than one terminal duct-lobular unit. The genetic changes are not identical, however, which suggests that genetic instability in these regions may play an early role in tumour development. We also confirm and extend our original observation of loss of the wild-type BRCA1 allele in some clones, and loss of the mutant allele in others, demonstrating that loss of either allele is a stochastic event.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6603298