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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2018.356    [Accepted]
Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan
Muhammad Usman Rashid1,2, Faiz Ali Khan1, Noor Muhammad1, Asif Loya3, Ute Hamann2
1Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), Lahore, Pakistan
2Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
3Department of Pathology, SKMCH&RC, Lahore, Pakistan
Correspondence  Muhammad Usman Rashid ,Tel: 92-423-5905000, Fax: 92-423-5945206, Email: usmanr@skm.org.pk
Received: June 14, 2018;  Accepted: October 10, 2018.  Published online: October 11, 2018.
Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan.
Materials and Methods
PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations.
A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127; 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5´ untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (<30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated.
Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.
Key words: Familial breast cancer, PALB2, Germ-line mutation, Pakistan
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