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Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population.
Breast Cancer Res Treat 2010; 119(2):295-303BC

Abstract

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.

Authors+Show Affiliations

Breast Cancer Institute, Cancer Hospital/Cancer Institute, Department of Oncology, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, 270 Dong'an Road, 200032, Shanghai, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19238535

Citation

Cao, A-Yong, et al. "Identification and Characterization of Two Novel Germ Line P53 Mutations in the non-LFS/non-LFL Breast Cancer Families in Chinese Population." Breast Cancer Research and Treatment, vol. 119, no. 2, 2010, pp. 295-303.
Cao AY, Jin W, Shi PC, et al. Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population. Breast Cancer Res Treat. 2010;119(2):295-303.
Cao, A. Y., Jin, W., Shi, P. C., Di, G. H., Shen, Z. Z., & Shao, Z. M. (2010). Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population. Breast Cancer Research and Treatment, 119(2), pp. 295-303. doi:10.1007/s10549-009-0349-6.
Cao AY, et al. Identification and Characterization of Two Novel Germ Line P53 Mutations in the non-LFS/non-LFL Breast Cancer Families in Chinese Population. Breast Cancer Res Treat. 2010;119(2):295-303. PubMed PMID: 19238535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification and characterization of two novel germ line p53 mutations in the non-LFS/non-LFL breast cancer families in Chinese population. AU - Cao,A-Yong, AU - Jin,Wei, AU - Shi,Peng-Cheng, AU - Di,Gen-hong, AU - Shen,Zhen-Zhou, AU - Shao,Zhi-Ming, Y1 - 2009/02/24/ PY - 2009/02/10/received PY - 2009/02/12/accepted PY - 2009/2/25/entrez PY - 2009/2/25/pubmed PY - 2010/3/11/medline SP - 295 EP - 303 JF - Breast cancer research and treatment JO - Breast Cancer Res. Treat. VL - 119 IS - 2 N2 - 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. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/19238535/Identification_and_characterization_of_two_novel_germ_line_p53_mutations_in_the_non_LFS/non_LFL_breast_cancer_families_in_Chinese_population_ L2 - https://doi.org/10.1007/s10549-009-0349-6 DB - PRIME DP - Unbound Medicine ER -