+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

No Evidence of BRCA1/2 genomic rearrangements in high-risk French-Canadian breast/ovarian cancer families



No Evidence of BRCA1/2 genomic rearrangements in high-risk French-Canadian breast/ovarian cancer families



Genetic Testing 10(2): 104-115



The discovery of deleterious mutations in the breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, has facilitated the identification of individuals at particularly high risk of these diseases. There is a wide variation between populations in the prevalence and related risks of various types of BRCA1/2 mutations, so estimates cannot be extrapolated to Canadians, especially not founder populations such as French- Canadians. Polymerase chain reaction (PCR)-based methods were used to detect the majority of these mutations. These approaches usually failed to detect large DNA rearrangements, which have been claimed to be involved in other populations in 5% to up to 36% of BRCA1-positive families. There is very little information about the contribution of this type of mutation in BRCA2-positive families. To investigate if our available mutation spectrum of BRCA1 and BRCA2 in high-risk French-Canadian breast/ovarian cancer families has been biased by PCR-based direct sequencing methods, we first used Southern blot analysis to test DNA samples from 61 affected/obligate carrier individuals from 58 families in which no BRCA1/2 deleterious mutation was found. Finally, 154 individuals from 135 BRCA1/2 nonconclusive families, including all those tested previously by Southern blot analysis, were tested with the new multiplex ligation probe amplification (MLPA) technique. These approaches failed to detect any rearrangement. Moreover, if the frequency of MLPA-detectable rearrangements in our cohort of 135 BRCA1/2 nonconclusive families was 2.2% or higher, we would have had a 95% or greater chance of observing at least one such rearrangement. As no rearrangements were identified, such large rearrangements must be quite rare in our population.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 049698672

Download citation: RISBibTeXText

PMID: 16792513

DOI: 10.1089/gte.2006.10.104


Related references

No evidence of recurent BRCA1/2 genomic rearrangement in high risk French-Canadian breast/ovarian cancer families. American Journal of Human Genetics 73(5): 241, 2003

Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families. Breast Cancer Research and Treatment 115(2): 315-323, 2009

Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families. Breast Cancer Research and Treatment 124(2): 579-584, 2010

Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families. Molecular Biology Reports 40(12): 6619-6623, 2013

Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families. Breast Cancer Research and Treatment 126(3): 705-716, 2011

Molecular epidemiology of BRCA1 and BRCA2 mutations in high risk French Canadian breast/ovarian cancer families. European Journal of Human Genetics 9(Suppl. 1): P0080, 2001

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families. Human Genetics 117(2-3): 119-132, 2005

Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. Journal of Medical Genetics 44(2): 107-121, 2007

Genetic variants and haplotype analyses of the ZBRK1/ZNF350 gene in high-risk non BRCA1/2 French Canadian breast and ovarian cancer families. International Journal of Cancer 122(1): 108-116, 2008

Screening for genomic rearrangements in BRCA1 and BRCA2 genes in Czech high-risk breast/ovarian cancer patients: high proportion of population specific alterations in BRCA1 gene. Breast Cancer Research and Treatment 124(2): 337-347, 2010

Prevalence of BRCA1 genomic rearrangements in a large cohort of Italian breast and breast/ovarian cancer families without detectable BRCA1 and BRCA2 point mutations. Genes Chromosomes and Cancer 45(9): 791-797, 2006

The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families. Cancer Research 68(17): 7006-7014, 2008

Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer. Bmc Cancer 9: 181, 2009

Identifying genomic rearrangements in BRCA1 and BRCA2 in high-risk individuals for hereditary breast and ovarian cancer. Journal of Clinical Oncology 29(27_Suppl): 163-163, 2016

Assessment of individuals with BRCA1 and BRCA2 large rearrangements in high-risk breast and ovarian cancer families. Breast Cancer Research and Treatment 145(3): 625-634, 2014