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Frequent somatic loss of BRCA1 in breast tumours from BRCA2 germ-line mutation carriers and vice versa

Staff, S.; Isola, J.J.; Johannsson, O.; Borg, Åke LU and Tanner, M.M. (2001) In British Journal of Cancer 85(8). p.1201-1205
Abstract
Breast cancer susceptibility genes BRCA1 and BRCA2 are tumour suppressor genes the alleles of which have to be inactivated before tumour development occurs. Hereditary breast cancers linked to germ-line mutations of BRCA1 and BRCA2 genes almost invariably show allelic imbalance (Al) at the respective loci. BRCA1 and BRCA2 are believed to take part in a common pathway in maintenance of genomic integrity in cells. We carried out Al and fluorescence in situ hybridization (FISH) analyses of BRCA2 in breast tumours from germline BRCA1 mutation carriers and vice versa. For comparison, 14 sporadic breast tumours were also studied. 8 of the 11 (73%) informative BRCA1 mutation tumours showed Al at the BRCA2 focus. 53% of these tumours showed a copy... (More)
Breast cancer susceptibility genes BRCA1 and BRCA2 are tumour suppressor genes the alleles of which have to be inactivated before tumour development occurs. Hereditary breast cancers linked to germ-line mutations of BRCA1 and BRCA2 genes almost invariably show allelic imbalance (Al) at the respective loci. BRCA1 and BRCA2 are believed to take part in a common pathway in maintenance of genomic integrity in cells. We carried out Al and fluorescence in situ hybridization (FISH) analyses of BRCA2 in breast tumours from germline BRCA1 mutation carriers and vice versa. For comparison, 14 sporadic breast tumours were also studied. 8 of the 11 (73%) informative BRCA1 mutation tumours showed Al at the BRCA2 focus. 53% of these tumours showed a copy number loss of the BRCA2 gene by FISH. 5 of the 6 (83%) informative BRCA2 mutation tumours showed Al at the BRCA1 locus. Half of the tumours (4/8) showed a physical deletion of the BRCA1 gene by FISH. Combined allelic loss of both BRCA1 and BRCA2 gene was seen in 12 of the 17 (71%) informative hereditary tumours, whereas copy number losses of both BRCA genes was seen in only 4/14 (29%) sporadic control tumours studied by FISH. In conclusion, the high prevalence of Al at BRCA1 in BRCA2 mutation tumours and vice versa suggests that somatic events occurring at the other breast cancer susceptibility gene locus may be selected in the cancer development. The mechanism resulting in Al at these loci seems more complex than a physical deletion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BRCA1, BRCA2, allelic imbalance, LOH, FISH
in
British Journal of Cancer
volume
85
issue
8
pages
1201 - 1205
publisher
Nature Publishing Group
external identifiers
  • wos:000171952700019
  • scopus:0035914252
ISSN
1532-1827
DOI
10.1054/bjoc.2001.2062
language
English
LU publication?
yes
id
7c667174-830d-4755-b049-fc3905e7c28d (old id 1118762)
date added to LUP
2008-07-15 09:45:29
date last changed
2018-01-07 06:06:06
@article{7c667174-830d-4755-b049-fc3905e7c28d,
  abstract     = {Breast cancer susceptibility genes BRCA1 and BRCA2 are tumour suppressor genes the alleles of which have to be inactivated before tumour development occurs. Hereditary breast cancers linked to germ-line mutations of BRCA1 and BRCA2 genes almost invariably show allelic imbalance (Al) at the respective loci. BRCA1 and BRCA2 are believed to take part in a common pathway in maintenance of genomic integrity in cells. We carried out Al and fluorescence in situ hybridization (FISH) analyses of BRCA2 in breast tumours from germline BRCA1 mutation carriers and vice versa. For comparison, 14 sporadic breast tumours were also studied. 8 of the 11 (73%) informative BRCA1 mutation tumours showed Al at the BRCA2 focus. 53% of these tumours showed a copy number loss of the BRCA2 gene by FISH. 5 of the 6 (83%) informative BRCA2 mutation tumours showed Al at the BRCA1 locus. Half of the tumours (4/8) showed a physical deletion of the BRCA1 gene by FISH. Combined allelic loss of both BRCA1 and BRCA2 gene was seen in 12 of the 17 (71%) informative hereditary tumours, whereas copy number losses of both BRCA genes was seen in only 4/14 (29%) sporadic control tumours studied by FISH. In conclusion, the high prevalence of Al at BRCA1 in BRCA2 mutation tumours and vice versa suggests that somatic events occurring at the other breast cancer susceptibility gene locus may be selected in the cancer development. The mechanism resulting in Al at these loci seems more complex than a physical deletion.},
  author       = {Staff, S. and Isola, J.J. and Johannsson, O. and Borg, Åke and Tanner, M.M.},
  issn         = {1532-1827},
  keyword      = {BRCA1,BRCA2,allelic imbalance,LOH,FISH},
  language     = {eng},
  number       = {8},
  pages        = {1201--1205},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Frequent somatic loss of BRCA1 in breast tumours from BRCA2 germ-line mutation carriers and vice versa},
  url          = {http://dx.doi.org/10.1054/bjoc.2001.2062},
  volume       = {85},
  year         = {2001},
}