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[演講] 5/8:王弘毅教授主講:腫瘤細胞的突變負荷 / Mutation Load in Cancer Cells

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張貼人:網站管理員公告日期:2017-04-24
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臺大基蛋所Medical Genetics & Genomics Monthly Seminar演講邀請

 

[講題]:腫瘤細胞的突變負荷 / Mutation Load in Cancer Cells

[講者]:王弘毅 教授CV詳如附件)

        台大臨床醫學研究所教授

 

[時間]5/8 (星期一) 上午 1120-1210

[地點]:醫學院基醫大樓 202講堂

[演講摘要]

During tumuriogenesis the cancer cells acquire several key mutations that drive rapid population growth. In the meantime, the accumulation of these driver alterations accompanied with hundreds or thousands of passenger mutations. If the overall effect of passengers is small or negligible, cancer progression can be described by simple mathematic model. In another extreme, if the proportion of highly deleterious mutation is large, majority of cancer cells would be defect with limited proliferative ability. Here, by monitoring the growth of randomly selected single cell clones derived from a HeLa cell population, we characterize the deleterious mutations that retard cell proliferation. The retardation effect is heritable as the progeny of slower growing cells also proliferate slowly. The main mutational event is copy number variations (CNVs), many of which being whole-chromosome aneuploidy. The rate of CNV generation is approximately 0.29 per division with 18% of fitness reduction per mutation on average. In the classical theory, the genetic load is twice the deleterious mutation rate; hence, the load on the HeLa cell population would be 0.58. Such a load is extremely high, certainly far larger than that of natural populations at << 1%. Our results suggest that the cancer cells must maintain a delicate balance to keep heterogeneity and to curb the relentlessly increased passenger mutations. Exploiting this character may help us to develop a new therapeutic regime for cancer.

 

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