Real‐time PCR‐based gene dosage assay for detecting BRCA1 rearrangements in breast–ovarian cancer families

@article{Barrois2004RealtimePG,
  title={Real‐time PCR‐based gene dosage assay for detecting BRCA1 rearrangements in breast–ovarian cancer families},
  author={Michel Barrois and Ivan Bi{\`e}che and Sylvie Mazoyer and M. H. Champ{\`e}me and Brigitte Bressac-de Paillerets and Rosette Lidereau},
  journal={Clinical Genetics},
  year={2004},
  volume={65}
}
BRCA1 and BRCA2 germline mutations, mainly point mutations and other small alterations, are responsible for most hereditary cases of breast–ovarian cancer. However, the observed frequency of BRCA1 alterations is lower than that predicted by linkage analysis. Several large BRCA1 rearrangements have been identified with a variety of technical approaches in some families. We have developed a gene dosage assay based on real‐time quantitative PCR and used it to extensively analyze 91 French families… 
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The results suggest the usefulness of screening for LGRs in BRCA genes in the Tunisian population and suggest that MLPA should be used in genetic testing programs.
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To investigate if the available mutation spectrum in high-risk French-Canadian breast/ovarian cancer families has been biased by PCR-based direct sequencing methods, Southern blot analysis was used to test DNA samples from 61 affected/obligate carrier individuals from 58 families in which no BRCA1/2 deleterious mutation was found.
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Women with mutations in the breast cancer genes BRCA1 or BRCA2 have an increased lifetime risk of developing breast, ovarian and other BRCA-associated cancers. However, the number of detected
Genomic rearrangements in BRCA1 and BRCA2: A literature review
TLDR
The detection of rearrangements in BRCA genes, especially BRCa1, offers a promising outlook for mutation screening in clinical practice, particularly in HBOC families that test negative for a germline mutation assessed by traditional methods.
Gross rearrangements in BRCA1 but not BRCA2 play a notable role in predisposition to breast and ovarian cancer in high-risk families of German origin.
TLDR
Evidence is provided that gross rearrangements within the BRCA1 gene locus may be as frequent as 3% in primarily mutation-negative tested high-risk familial breast and ovarian cancer of German ancestry, while large alterations involving the B RCA2 locus do not appear to play a significant role in disease etiology.
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