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Open Access Research article

Constitutional CHEK2 mutations are infrequent in early-onset and familial breast/ovarian cancer patients from Pakistan

Muhammad U Rashid12, Noor Muhammad1, Saima Faisal1, Asim Amin3 and Ute Hamann2*

Author Affiliations

1 Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan

2 Deutsches Krebsforschungszentrum (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany

3 Levine Cancer Institute, Carolinas Medical Center, Charlotte, USA

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BMC Cancer 2013, 13:312  doi:10.1186/1471-2407-13-312

Published: 27 June 2013



Less than 20% of Pakistani women with early-onset or familial breast/ovarian cancer harbor germ line mutations in the high-penetrance genes BRCA1, BRCA2 and TP53. Thus, mutations in other genes confer genetic susceptibility to breast cancer, of which CHEK2 is a plausible candidate. CHEK2 encodes a checkpoint kinase, involved in response to DNA damage.


In the present study we assessed the prevalence of CHEK2 germ line mutations in 145 BRCA1/2-negative early-onset and familial breast/ovarian cancer patients from Pakistan (Group 1). Mutation analysis of the complete CHEK2 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments.


Two potentially deleterious missense mutations, c.275C>G (p.P92R) and c.1216C>T, (p.R406C), were identified (1.4%). The c.275C>G mutation is novel and has not been described in other populations. It was detected in a 30-year-old breast cancer patient with a family history of breast and multiple other cancers. The c.1216C>T mutation was found in a 34-year-old ovarian cancer patient from a family with two breast cancer cases. Both mutations were not detected in 229 recently recruited BRCA1/2-negative high risk patients (Group 2).


Our findings suggest that CHEK2 mutations may not contribute significantly to breast/ovarian cancer risk in Pakistani women.

CHEK2; Germ line mutations; Early-onset and familial breast cancer; Pakistan