https://scholars.lib.ntu.edu.tw/handle/123456789/478415
標題: | Multimodel assessment of BRCA1 mutations in Taiwanese (ethnic Chinese) women with early-onset, bilateral or familial breast cancer | 作者: | WEN-HUNG KUO PO-HAN LIN Huang A.-C. YIN-HSIU CHIEN Liu T.-P. YEN-SHEN LU Bai L.-Y. Sargeant A.M. CHING-HUNG LIN ANN-LII CHENG FON-JOU HSIEH WUH-LIANG HWU KING-JEN CHANG |
公開日期: | 2012 | 卷: | 57 | 期: | 2 | 起(迄)頁: | 130-138 | 來源出版物: | Journal of Human Genetics | 摘要: | Although evidence suggests an importance of genetic factors in the development of breast cancer in Taiwanese (ethnic Chinese) women, including a high incidence of early-onset and secondary contralateral breast cancer, a major breast cancer predisposition gene, BRCA1, has not been well studied in this population. In fact, the carcinogenic impacts of many genetic variants of BRCA1 are unknown and classified as variants of uncertain significance (VUS). It is therefore important to establish a method to characterize the BRCA1 VUSs and understand their role in Taiwanese breast cancer patients. Accordingly, we developed a multimodel assessment strategy consisting of a prescreening portion and a validated functional assay to study breast cancer patients with early-onset, bilateral or familial breast cancer. We found germ-line BRCA1 mutations in 11.1% of our cohort and identified one novel missense mutation, c.5191C>A. Two genetic variants were initially classified as VUSs (c.1155C>T and c.5191C>A). c.1155C>T is not predicted to be deleterious in the prescreening portion of our assessment strategy. c.5191C>A, on the other hand, causes p.T1691K, which is predicted to have high deleterious probability because of significant structural alteration, a high deleterious score in the predictive programs and, clinically, triple negative characteristics in breast tumors. This mutant is confirmed by transcription activation and yeast growth-inhibition assays. In conclusion, we show as high a prevalence of germ-line BRCA1 mutation in high-risk Taiwanese patients as in Caucasians and demonstrate a useful strategy for studying BRCA1 VUSs. ? 2012 The Japan Society of Human Genetics All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84863258276&doi=10.1038%2fjhg.2011.142&partnerID=40&md5=9130541d62ac8e6a8c447058622b7cc7 https://scholars.lib.ntu.edu.tw/handle/123456789/478415 |
ISSN: | 1434-5161 | DOI: | 10.1038/jhg.2011.142 | SDG/關鍵字: | adult; article; breast cancer; cancer susceptibility; Chinese; clinical article; familial cancer; female; gene mutation; genetic variability; human; missense mutation; oncogene; transcription initiation; Adult; Amino Acid Motifs; Asian Continental Ancestry Group; Base Sequence; BRCA1 Protein; Breast Neoplasms; Carcinoma, Ductal, Breast; Computational Biology; DNA Mutational Analysis; Female; Genetic Association Studies; Germ-Line Mutation; HEK293 Cells; Humans; Middle Aged; Models, Molecular; Molecular Sequence Data; Polymorphism, Genetic; Protein Structure, Tertiary; Recombinant Fusion Proteins; Saccharomyces cerevisiae; Sequence Alignment; Taiwan |
顯示於: | 醫學系 |
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