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Detection of Germline BRCA1 Mutations in Breast Cancer Patients by Quantitative Messenger RNA in situ Hybridization

Kainu, Tommi; Kononen, Juha; Johansson, Oskar; Olsson, Håkan LU ; Borg, Åke LU and Isola, Jorma LU (1996) In Cancer Research p.2912-2915
Abstract
Mutations in the breast cancer susceptibility gene 1 (BRCA1) may account for one half of all familial breast cancers. Because of the wide spectrum of different germline mutations, identification of BRCA1 mutation carriers using current techniques is laborious and difficult. The majority of the identified mutations, however, lead to aberrant expression of the gene product in tumor tissue, potentially allowing the detection of BRCA1-linked breast cancers using simple histochemical techniques. We performed quantitative mRNA in situ hybridization analysis on archival paraffin-embedded tumor specimens from 25 patients with characterized germline BRCA1 mutations or linkage and from 29 patients with sporadic breast cancers. BRCA1 mRNA levels were... (More)
Mutations in the breast cancer susceptibility gene 1 (BRCA1) may account for one half of all familial breast cancers. Because of the wide spectrum of different germline mutations, identification of BRCA1 mutation carriers using current techniques is laborious and difficult. The majority of the identified mutations, however, lead to aberrant expression of the gene product in tumor tissue, potentially allowing the detection of BRCA1-linked breast cancers using simple histochemical techniques. We performed quantitative mRNA in situ hybridization analysis on archival paraffin-embedded tumor specimens from 25 patients with characterized germline BRCA1 mutations or linkage and from 29 patients with sporadic breast cancers. BRCA1 mRNA levels were invariably low in tumors from BRCA1 mutation carriers. Normal breast epithelium surrounding the BRCA1 tumors showed higher mRNA levels than the tumor tissue, indicating that the low mRNA levels were due to somatic inactivation of the wild-type BRCA1 allele in the tumor tissue. The expression levels in the sporadic tumors were, on average, six times higher than in the BRCA1 tumors (P < 0.0001). The difference allowed identification of BRCA1-mutated and sporadic tumors with more than 95% specificity and sensitivity. We conclude that the analysis of BRCA1 gene expression by mRNA in situ hybridization may be useful in screening for patients with BRCA1-linked breast cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
pages
2912 - 2915
publisher
American Association for Cancer Research Inc.
external identifiers
  • scopus:0029936995
ISSN
1538-7445
language
English
LU publication?
yes
id
1ebd7664-b170-45df-8d06-1918fa963bac (old id 34138)
alternative location
http://cancerres.aacrjournals.org/cgi/reprint/56/13/2912
date added to LUP
2007-06-15 12:02:01
date last changed
2017-01-01 07:52:41
@article{1ebd7664-b170-45df-8d06-1918fa963bac,
  abstract     = {Mutations in the breast cancer susceptibility gene 1 (BRCA1) may account for one half of all familial breast cancers. Because of the wide spectrum of different germline mutations, identification of BRCA1 mutation carriers using current techniques is laborious and difficult. The majority of the identified mutations, however, lead to aberrant expression of the gene product in tumor tissue, potentially allowing the detection of BRCA1-linked breast cancers using simple histochemical techniques. We performed quantitative mRNA in situ hybridization analysis on archival paraffin-embedded tumor specimens from 25 patients with characterized germline BRCA1 mutations or linkage and from 29 patients with sporadic breast cancers. BRCA1 mRNA levels were invariably low in tumors from BRCA1 mutation carriers. Normal breast epithelium surrounding the BRCA1 tumors showed higher mRNA levels than the tumor tissue, indicating that the low mRNA levels were due to somatic inactivation of the wild-type BRCA1 allele in the tumor tissue. The expression levels in the sporadic tumors were, on average, six times higher than in the BRCA1 tumors (P &lt; 0.0001). The difference allowed identification of BRCA1-mutated and sporadic tumors with more than 95% specificity and sensitivity. We conclude that the analysis of BRCA1 gene expression by mRNA in situ hybridization may be useful in screening for patients with BRCA1-linked breast cancer.},
  author       = {Kainu, Tommi and Kononen, Juha and Johansson, Oskar and Olsson, Håkan and Borg, Åke and Isola, Jorma},
  issn         = {1538-7445},
  language     = {eng},
  pages        = {2912--2915},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Detection of Germline BRCA1 Mutations in Breast Cancer Patients by Quantitative Messenger RNA in situ Hybridization},
  year         = {1996},
}