Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population

Autor: Zhenzhou Shen, Zhi-Ming Shao, A-Yong Cao, Genhong Di, Peng-Cheng Shi, Wei Jin
Rok vydání: 2009
Předmět:
Cancer Research
Time Factors
DNA Mutational Analysis
Apoptosis
medicine.disease_cause
Polymerase Chain Reaction
Germline
Li-Fraumeni Syndrome
Risk Factors
Age of Onset
skin and connective tissue diseases
Chromatography
High Pressure Liquid
Genetics
Mutation
medicine.diagnostic_test
BRCA1 Protein
Intracellular Signaling Peptides and Proteins
Exons
Flow Cytometry
Pedigree
Gene Expression Regulation
Neoplastic
Phenotype
Oncology
Female
Breast disease
Cyclin-Dependent Kinase Inhibitor p27
Adult
Transcriptional Activation
China
Tumor suppressor gene
Blotting
Western
Breast Neoplasms
Biology
Transfection
Germline mutation
Breast cancer
Asian People
Cell Line
Tumor
medicine
Humans
Genetic Predisposition to Disease
Germ-Line Mutation
Genetic testing
BRCA2 Protein
Cancer
medicine.disease
Introns
Case-Control Studies
Tumor Suppressor Protein p53
Apoptosis Regulatory Proteins
Zdroj: Breast cancer research and treatment. 119(2)
ISSN: 1573-7217
Popis: Germ line mutations in the tumor suppressor gene, p53, are known to cause Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL). We sought to identify p53 germ line mutations in potential hereditary breast cancer patients without LFS/LFL phenotype, which will help us establish the genetic testing strategy for p53 in Chinese high-risk breast cancer families. We screened all coding exons and intron-exon boundaries of p53 in 240 women with early-onset breast cancer or affected relatives from four breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Additionally, three cell lines (H1299, MCF-7, and MDA-MB-231) were transfected with pEGFP-N1-only or pEGFP-N1 vectors expressing either wild-type or two novel identified mutant p53. And then we performed flow cytometry analysis in the transfected cells to determine the status of cell apoptosis, and real-time PCR as well as western blot analysis to ascertain the expression of p53, p21, and p27. Two novel germ line mutations (563T > C and 643_660del18) were detected in two independent families. Neither of them, however, was present in the 768 normal controls. Functional assays revealed that the ability to trigger cell apoptosis and transcriptional activation of target gene under similar expression of p53 were lower in two mutants versus wild-type p53. Deleterious mutations of p53 seemed to be responsible for approximately 1% of non-BRCA1/BRCA2 hereditary breast cancer in Chinese population, and our findings suggested that p53 should be included in genetic testing of Chinese non-LFS/non-LFL high-risk breast cancer families.
Databáze: OpenAIRE
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