RISS 검색 - 국내학술지논문 상세보기

다국어 초록 (Multilingual Abstract)

Purpose 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.
Results 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.
Conclusion Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

참고문헌 (Reference)

1 Silvestri V, "Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene" 123 : 210-218, 2017

2 Park JS, "Variants of cancer susceptibility genes in Korean BRCA1/2 mutationnegative patients with high risk for hereditary breast cancer" 18 : 83-, 2018

3 Cao AY, "The prevalence of PALB2 germline mutations in BRCA1/BRCA2negative Chinese women with early onset breast cancer or affected relatives" 114 : 457-462, 2009

4 Heikkinen T, "The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype" 15 : 3214-3222, 2009

5 Janatova M, "The PALB2 gene is a strong candidate for clinical testing in BRCA1-and BRCA2-negative hereditary breast cancer" 22 : 2323-2332, 2013

6 Singh J, "Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel : prevalence of BRCA1/2 and non-BRCA mutations" 170 : 189-196, 2018

7 Kuusisto KM, "Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2founder mutation-negative breast and/or ovarian cancer individuals" 13 : R20-, 2011

8 Rashid MU, "Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients" 11 : 307-311, 2012

9 Phuah SY, "Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore" 8 : e73638-, 2013

10 Thompson ER, "Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls" 17 : 111-, 2015