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BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features

Koul, A. LU ; Malander, S. LU ; Loman, N. LU ; Pejovic, T.; Heim, S. LU ; Willen, R.; Johannsson, O. LU ; Olsson, H. LU ; Ridderheim, M. LU and Borg Å, Å. (2000) In International Journal of Gynecological Cancer 10(4). p.289-295
Abstract

We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29... (More)

We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
BRCA1 • BRCA2 • chromosome 6 • cytogenetics • karyotype • ovarian cancer
in
International Journal of Gynecological Cancer
volume
10
issue
4
pages
7 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:11240689
  • scopus:0033813379
ISSN
1048-891X
DOI
10.1046/j.1525-1438.2000.010004289.x
language
English
LU publication?
yes
id
4f2ff24c-a35c-4e4c-b728-912ae604293e (old id 1117159)
date added to LUP
2008-07-03 08:41:05
date last changed
2017-01-01 04:27:58
@article{4f2ff24c-a35c-4e4c-b728-912ae604293e,
  abstract     = {<p>We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.</p>},
  author       = {Koul, A. and Malander, S. and Loman, N. and Pejovic, T. and Heim, S. and Willen, R. and Johannsson, O. and Olsson, H. and Ridderheim, M. and Borg Å, Å.},
  issn         = {1048-891X},
  keyword      = {BRCA1 • BRCA2 • chromosome 6 • cytogenetics • karyotype • ovarian cancer},
  language     = {eng},
  number       = {4},
  pages        = {289--295},
  publisher    = {Wiley-Blackwell},
  series       = {International Journal of Gynecological Cancer},
  title        = {BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features},
  url          = {http://dx.doi.org/10.1046/j.1525-1438.2000.010004289.x},
  volume       = {10},
  year         = {2000},
}