The Relative Contribution of Point Mutations and Genomic Rearrangements in <i>BRCA1</i> and <i>BRCA2</i> in High-Risk Breast Cancer Families

Palma, Maurizia Dalla; Domchek, Susan M.; Stopfer, Jill E.; Erlichman, Julie; Siegfried, Jill D.; Tigges-Cardwell, Jessica; Mason, Bernard A.; Rebbeck, Timothy R.; Nathanson, Katherine L.

doi:10.1158/0008-5472.can-08-0599

Cited by 99 publications

(64 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Genomic rearrangements represent 40% of the BRCA1 mutations in a northern Italian population with a reported founder effect [10]. In another study conducted in non-Ashkenazi Jewish group, BRCA1/2 genomic rearrangements constituted 18% of all the mutations identified [15]. Our results suggest that BRCA1 genomic rearrangements exist but do not contribute to a significant BRCA1-associated risk in the Nigerian population.…”

Section: Discussionmentioning

confidence: 51%

Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population

Zhang

Fackenthal

Huo

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

BRCA1/2 germline mutations predispose to breast and ovarian cancer. Large genomic rearrangements (LGRs) have widened the mutational spectrum of the BRCA1 gene, but the frequencies vary in different populations. In this study, we want to determine the spectrum of LGRs in BRCA1 gene in Nigerian breast cancer patients. The multiplex ligation-dependent probe amplification (MLPA) assay was used to screen BRCA1 rearrangements in 352 patients who previously tested negative for BRCA1 and BRCA2 point mutations and small insertions/deletions. Positive MLPA result was confirmed and located by long-range PCR. The breakpoints of the candidate rearrangement were characterized by sequencing. A novel deletion of BRCA1 exon 21 (c.5277 + 480_5332 + 672del) was detected in 1 out of 352 Nigerian breast cancer patients (0.3% occurrence frequency). Further analysis of breakpoints revealed that the deletion involves two Alu-elements: one AluSg in intron 20 and the AluY in intron 21. These data suggest that while BRCA1 genomic rearrangement exists, they do not contribute significantly to BRCA1-associated risk in the Nigerian population.

show abstract

Section: Discussionmentioning

confidence: 51%

Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population

Zhang

Fackenthal

Huo

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…These have estimated the prevalence of BRCA1 and BRCA2 mutations in such high-risk families from 20 to 67% ( (Shih et al, 2000;Fackenthal and Olopade, 2007;Palma et al, 2008), and numerous others), where variation is mainly due to study design and population genetic pool, that is founder populations tend to present higher frequencies. There are also numerous studies with populations selected for age of onset.…”

Section: Discussionmentioning

confidence: 99%

Contribution of BRCA1 germ-line mutations to breast cancer in Greece: a hospital-based study of 987 unselected breast cancer cases

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: In most Western populations, 5 -10% of all breast cancer cases can be attributed to major genetic factors such as predisposing mutations in BRCA1 and BRCA2, with early-onset cases generally considered as an indicator of genetic susceptibility. Specific BRCA1 and BRCA2 mutations or different mutation frequencies have been identified in specific populations and ethnic groups. Previous studies in Greek breast and/or ovarian cancer patients with family history have shown that four specific BRCA1 mutations, c.5266dupC, G1738R, and two large genomic rearrangements involving deletions of exons 20 and 24, have a prominent function in the population's BRCA1 and BRCA2 mutation spectrum. METHODS: To estimate the frequency of the above mutations in unselected Greek breast cancer women, we screened 987 unselected cases independently of their family history, collected from major Greek hospitals. RESULTS: Of the 987 patients, 26 (2.6%) were found to carry one of the above mutations in the BRCA1 gene: 13 carried the c.5266dupC mutation (1.3%), 6 carried the exon 24 deletion (0.6%), 3 carried the exon 20 deletion (0.3%), and 4 carried the G1738R mutation (0.4%). Among 140 patients with early-onset breast cancer (o40 years), 14 carried one of the four mutations (10.0%). CONCLUSION: These results suggest that a low-cost genetic screening for only the four prominent BRCA1 mutations may be advisable to all early-onset breast cancer patients of Greek origin.

show abstract

“…1,5 Deleterious large rearrangement BRCA mutations are not detectable by standard sequencing. [6][7][8] The prevalence of BRCA1 ex9-12del, a recurrent large rearrangement mutation initially identified in a small MexicanAmerican high-risk clinic cohort, is unknown. 2 The risk for BRCA mutation carriers to develop BC varies from 57% by age 70 years 9 to 85% lifetime…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Type ofBRCAMutations in Hispanics Undergoing Genetic Cancer Risk Assessment in the Southwestern United States: A Report From the Clinical Cancer Genetics Community Research Network

Weitzel

Clague

Martir-Negron

et al. 2013

JCO

145

160

View full text Add to dashboard Cite

A B S T R A C T PurposeTo determine the prevalence and type of BRCA1 and BRCA2 (BRCA) mutations among Hispanics in the Southwestern United States and their potential impact on genetic cancer risk assessment (GCRA). Patients and MethodsHispanics (n ϭ 746) with a personal or family history of breast and/or ovarian cancer were enrolled in an institutional review board-approved registry and received GCRA and BRCA testing within a consortium of 14 clinics. Population-based Hispanic breast cancer cases (n ϭ 492) enrolled in the Northern California Breast Cancer Family Registry, negative by sequencing for BRCA mutations, were analyzed for the presence of the BRCA1 ex9-12del large rearrangement. ResultsDeleterious BRCA mutations were detected in 189 (25%) of 746 familial clinic patients (124 BRCA1, 65 BRCA2); 21 (11%) of 189 were large rearrangement mutations, of which 62% (13 of 21) were BRCA1 ex9-12del. Nine recurrent mutations accounted for 53% of the total. Among these, BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic-and population-based cohorts in the United States. ConclusionBRCA mutations were prevalent in the largest study of Hispanic breast and/or ovarian cancer families in the United States to date, and a significant proportion were large rearrangement mutations. The high frequency of large rearrangement mutations warrants screening in every case. We document the first Mexican founder mutation (BRCA1 ex9-12del), which, along with other recurrent mutations, suggests the potential for a cost-effective panel approach to ancestry-informed GCRA.

show abstract

The Relative Contribution of Point Mutations and Genomic Rearrangements in BRCA1 and BRCA2 in High-Risk Breast Cancer Families

Cited by 99 publications

References 54 publications

Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population

Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population

Contribution of BRCA1 germ-line mutations to breast cancer in Greece: a hospital-based study of 987 unselected breast cancer cases

Prevalence and Type ofBRCAMutations in Hispanics Undergoing Genetic Cancer Risk Assessment in the Southwestern United States: A Report From the Clinical Cancer Genetics Community Research Network

Contact Info

Product

Resources

About