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Allelic transcripts dosage effect in morphologically normal ovarian cells from heterozygous carriers of a BRCA1/2 French Canadian founder mutation
- Source :
- Cancer prevention research (Philadelphia, Pa.). 5(5)
- Publication Year :
- 2012
-
Abstract
- We hypothesized that the transcriptome of primary cultures of morphologically normal ovarian surface epithelial cells could be altered by the presence of a heterozygous BRCA1 or BRCA2 mutation. We aimed to discover early events associated with ovarian carcinogenesis, which could represent putative targets for preventive strategies of this silent killer tumor. We identified the first molecular signature associated with French Canadian BRCA1 or BRCA2 founder mutations in morphologically normal ovarian epithelial cells. We discovered that wild-type and mutated BRCA2 allelic transcripts were expressed not only in morphologically normal but also in tumor cells from BRCA2-8765delAG carriers. Further analysis of morphologically normal ovarian and tumor cells from BRCA1-4446C>T carriers lead to the same observation. Our data support the idea that one single hit in BRCA1 or BRCA2 is sufficient to alter the transcriptome of phenotypically normal ovarian epithelial cells. The highest level of BRCA2-mutated allele transcript expression was measured in cells originating from the most aggressive ovarian tumor. The penetrance of the mutation and the aggressiveness of the related tumor could depend on a dosage effect of the mutated allele transcript. Cancer Prev Res; 5(5); 765–77. ©2012 AACR.
- Subjects :
- Adult
Cancer Research
Canada
Heterozygote
endocrine system diseases
DNA Mutational Analysis
Genes, BRCA2
Gene Dosage
Genes, BRCA1
Penetrance
Biology
Validation Studies as Topic
medicine.disease_cause
Transcriptome
Ovarian tumor
medicine
Humans
RNA, Messenger
Allele
skin and connective tissue diseases
Gene
Alleles
Cells, Cultured
Aged
Mutation
Ovary
Quebec
Heterozygote advantage
Middle Aged
Molecular biology
female genital diseases and pregnancy complications
Founder Effect
Oncology
Female
Founder effect
Subjects
Details
- ISSN :
- 19406215
- Volume :
- 5
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cancer prevention research (Philadelphia, Pa.)
- Accession number :
- edsair.doi.dedup.....bc06a66faa65e76a0b348b56efd9dd0a