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• Recurrent BRCA1 mutation among Malay breast/ovarian cancer patients
  Ann SG Lee
  Published on: 27 April 2016

• Published on: 27 April 2016

  Recurrent BRCA1 mutation among Malay breast/ovarian cancer patients

  • Ann SG Lee, Senior Scientist
  • Other Contributors:
    • Gay-Hui Ho

  Dear Editor

  We read with great interest the report by Sng et al. [1] in which the authors reported that the BRCA1 frameshift mutation 2845insA could be a founder mutation in Malay breast or ovarian cancer patients in Singapore. This mutation results in protein truncation at codon 914.

  We would like to take this opportunity to draw the readers’ attention to our work on BRCA1 mutations among Singapo...

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  Dear Editor

  We read with great interest the report by Sng et al. [1] in which the authors reported that the BRCA1 frameshift mutation 2845insA could be a founder mutation in Malay breast or ovarian cancer patients in Singapore. This mutation results in protein truncation at codon 914.

  We would like to take this opportunity to draw the readers’ attention to our work on BRCA1 mutations among Singapore breast cancer patients. In the initial study comprising 43 women with early-onset breast cancer (before age 36), the same deleterious mutation as that reported by Sng et al. was identified in 2 of 7 unrelated Malay women.[2] This led to a further study on 49 unrelated Malay breast cancer patients, the results of which were published in Human Mutation in August 2003.[3] Three patients and three relatives of these patients carried the frameshift mutation. Haplotype analysis using the microsatellite markers D17S855, D17S1323 and D17S1325 showed a common haplotype for these cases and their relatives with the mutation. This common haplotype was not seen in any of the controls in both studies.[1,3]

  In the report by Sng et al. [1], haplotype analysis of family members of the six patients with the mutation was not done, as samples from relatives were not available then, but this work is currently underway. Haplotype analysis of the parents of two of the patients in our study,[3] showed segregation of haplotypes to the patients, supporting the suggestion that this may be a founder mutation.

  In contrast to the studies on Singaporean Malays, this 2845insA mutation was not detected in any of the 16 Malay breast cancer patients from Malaysia.[4] However, this may be due to the small sample size in that study.

  The results of Sng et al. are consistent with ours, which strongly suggest that the 2845insA mutation is a founder mutation in breast cancer patients of Malay ethnicity. Indeed, once validated with a larger cohort of Malays, comprising both breast cancer patients and normal subjects, these results would facilitate genetic counselling and screening of Malays.

  References

  (1) Sng J-H, Ali AB, Lee SC, Wong JEL, Blake V, Sharif A, Cross G, Iau PTC. BRCA1 c.2845insA is a recurring mutation with a founder effect in Singapore Malay women with early-onset breast/ovarian cancer. J Med Genet 2003;40:e117.

  (2) Ho GH, Phang BH, Ng IS, Law HY, Soo KC, Ng EH. Novel germline BRCA1 mutations detected in women in Singapore who developed breast carcinoma before the age of 36 years. Cancer 2000;89:811-6.

  (3) Lee ASG, Ho GH, Oh PC, Balram C, Ooi LL, Lim DTH, Wong CY, Hong GS. Founder mutation in the BRCA1 gene in Lalay breast cancer patients from Singapore. Hum Mutat 2003;22:178.

  (4) Balraj P, Khoo AS, Volpi L, Tan JA, Nair S, Abdullah H. Mutation analysis of the BRCA1 gene in Malaysian breast cancer patients. Singapore Med J 2002;43:194-7.

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  Conflict of Interest:
  None declared.

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