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

Noor Akmal Sharifah, Nurismah Md Isa, Han Chung Lee, Aziz Nur Aisyah, Ching Huat Clarence-Ko, Ismail Naqiyah, Rohaizak Muhammad, Fuad Ismail, A. Rahman A. Jamal, Zarina Abdul Latiff, Emran Nor Aina, Kitan Normayah, Abdullah Nor Hisham

Research output: Contribution to journalArticle

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Abstract

Background: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. Methods: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Results: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. Conclusion: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.

Original languageEnglish
Pages (from-to)442-447
Number of pages6
JournalCancer Epidemiology
Volume34
Issue number4
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Breast Neoplasms
Malaysia
Neoplasm Genes
Mutation
Exons
BRCA2 Gene
BRCA1 Gene
Germ-Line Mutation
Multiplex Polymerase Chain Reaction
Genetic Testing
Point Mutation
Referral and Consultation
Polymerase Chain Reaction
Incidence

Keywords

  • BRCA1
  • Large genomic rearrangements
  • Malaysia
  • MLPA
  • QPCR
  • Sporadic breast cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Epidemiology

Cite this

Sharifah, N. A., Md Isa, N., Lee, H. C., Aisyah, A. N., Clarence-Ko, C. H., Naqiyah, I., ... Nor Hisham, A. (2010). Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer. Cancer Epidemiology, 34(4), 442-447. https://doi.org/10.1016/j.canep.2010.04.010

Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer. / Sharifah, Noor Akmal; Md Isa, Nurismah; Lee, Han Chung; Aisyah, Aziz Nur; Clarence-Ko, Ching Huat; Naqiyah, Ismail; Muhammad, Rohaizak; Ismail, Fuad; A. Jamal, A. Rahman; Abdul Latiff, Zarina; Nor Aina, Emran; Normayah, Kitan; Nor Hisham, Abdullah.

In: Cancer Epidemiology, Vol. 34, No. 4, 08.2010, p. 442-447.

Research output: Contribution to journalArticle

Sharifah, Noor Akmal ; Md Isa, Nurismah ; Lee, Han Chung ; Aisyah, Aziz Nur ; Clarence-Ko, Ching Huat ; Naqiyah, Ismail ; Muhammad, Rohaizak ; Ismail, Fuad ; A. Jamal, A. Rahman ; Abdul Latiff, Zarina ; Nor Aina, Emran ; Normayah, Kitan ; Nor Hisham, Abdullah. / Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer. In: Cancer Epidemiology. 2010 ; Vol. 34, No. 4. pp. 442-447.
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abstract = "Background: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. Methods: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Results: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. Conclusion: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.",
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AU - Clarence-Ko, Ching Huat

AU - Naqiyah, Ismail

AU - Muhammad, Rohaizak

AU - Ismail, Fuad

AU - A. Jamal, A. Rahman

AU - Abdul Latiff, Zarina

AU - Nor Aina, Emran

AU - Normayah, Kitan

AU - Nor Hisham, Abdullah

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N2 - Background: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. Methods: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Results: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. Conclusion: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.

AB - Background: The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer. Methods: Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Results: Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients. Conclusion: These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.

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