Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer

Na, Sharifah; Nurismah, Isa; Lee, Han Chung; Aisyah, Aziz Nur; Clarence-Ko, Ching Huat; Naqiyah, I; Muhammad, Rohaizak; Ismail, Fuad; Jamal, A. Rahman A.; Latiff, Zarina Abdul; Aina, E. N.; Normayah, Kitan; Abdullah, Noor Hisham

doi:10.1016/j.canep.2010.04.010

Cited by 11 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study the authors demonstrated through MLPA two different rearrangements validated by qPCR that resulted to be localized outside BRCA1.In addition, the LGRs do not segregate with breast cancer in two families (family 71 for exons 3-6 and family 59 for exon10; Table 2), revealing no association of the amplification with the pathology. Recently, in an Asian sporadic breast cancer patient, an amplification of exon 10 of BRCA1 has been reported [28] which is similar to the one found in this study. Amplification of BRCA1 exons 3-6 has not been described to date.…”

Section: Discussionsupporting

confidence: 89%

Genomic rearrangements of the BRCA1 gene in Chilean breast cancer families: an MLPA analysis

Sánchez

Faundez

Carvallo

2011

Breast Cancer Res Treat

View full text Add to dashboard Cite

Point mutations and small deletions and insertions in BRCA1 and BRCA2 genes are responsible of about 20% of hereditary breast cancer cases in Chilean population. Studies in other populations have identified the amplification and/or deletion of one or more exons in these genes as the cause of the disease. In this study the authors determined the presence of these types of alterations in BRCA1 and BRCA2, in 74 Chilean families with breast/ovarian cancer that were negative for germline mutations in these genes. Since these alterations are not detectable using the conventional PCR-based methods, the authors use MLPA (multiplex ligation-dependent probe amplification) to detect amplifications and/or deletions in BRCA1 and BRCA2 genes. The authors identified two different alterations in BRCA1: exon 10 duplication in one family and amplification of exons 3, 5, and 6 in two families. Duplication of exon 10 contains intronic adjacent sequences suggesting gene duplication. The second rearrangement consist of a 4 times amplification of a fragment containing exons 3, 5, and 6 joined together with no introns, suggesting the presence of a processed pseudogene. No alterations were detected in BRCA2. In order to validate the MLPA results and characterize the genomic alterations the authors performed qPCR, long range PCR, and sequencing.

show abstract

Section: Discussionsupporting

confidence: 89%

Genomic rearrangements of the BRCA1 gene in Chilean breast cancer families: an MLPA analysis

Sánchez

Faundez

Carvallo

2011

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…However, there have been relatively few reports of such large genomic rearrangements from Asia, with only seven reports involving a total of 649 patients from Hong Kong, Singapore, Korea, Japan and Malaysia [3][4][5][6][7][8][9]. This is in part because there have been relatively few studies involving comprehensive analysis of BRCA1 and BRCA2 in Asia, and to date, few Asian countries have had the resources and finances for breast cancer genetic counseling and genetic testing services.…”

Section: Introductionmentioning

confidence: 84%

Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families

Kang

Mariapun

Phuah

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.

show abstract

“…In BRCA1 , LGRs have been detected with varying frequencies among patients with breast or ovarian cancer. 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 In a study of 805 Dutch families with a known predisposition for breast and/or ovarian cancer, those without identified pathogenic BRCA1 or BRCA2 mutations by conventional mutation screening methods (661) were assessed for BRCA1 germline LGRs. 23 A total of 33 families with a deletion or duplication event in BRCA1 were identified, representing 27% of the total 121 pathogenic BRCA1 mutations.…”

Section: Brca Testing: An Overviewmentioning

confidence: 99%

New challenges for BRCA testing: a view from the diagnostic laboratory

Wallace

2016

Eur J Hum Genet

View full text Add to dashboard Cite

Increased demand for BRCA testing is placing pressures on diagnostic laboratories to raise their mutation screening capacity and handle the challenges associated with classifying BRCA sequence variants for clinical significance, for example interpretation of pathogenic mutations or variants of unknown significance, accurate determination of large genomic rearrangements and detection of somatic mutations in DNA extracted from formalin-fixed, paraffin-embedded tumour samples. Many diagnostic laboratories are adopting next-generation sequencing (NGS) technology to increase their screening capacity and reduce processing time and unit costs. However, migration to NGS introduces complexities arising from choice of components of the BRCA testing workflow, such as NGS platform, enrichment method and bioinformatics analysis process. An efficient, cost-effective accurate mutation detection strategy and a standardised, systematic approach to the reporting of BRCA test results is imperative for diagnostic laboratories. This review covers the challenges of BRCA testing from the perspective of a diagnostics laboratory.

show abstract

Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer

Cited by 11 publications

References 22 publications

Genomic rearrangements of the BRCA1 gene in Chilean breast cancer families: an MLPA analysis

Genomic rearrangements of the BRCA1 gene in Chilean breast cancer families: an MLPA analysis

Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families

New challenges for BRCA testing: a view from the diagnostic laboratory

Contact Info

Product

Resources

About