| Autor: |
Yong Tao, Jue Ruan, Shiou-Hwei Yeh, Xuemei Lu, Yu Wang, Weiwei Zhai, Jun Cai, Shaoping Ling, Qiang Gong, Zecheng Chong, Zhengzhong Qu, Qianqian Li, Jiang Liu, Jin Yang, Caihong Zheng, Changqing Zeng, Hurng-Yi Wang, Jing Zhang, Sheng-Han Wang, Lingtong Hao |
| Předmět: |
|
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 7/19/2011, Vol. 108 Issue 29, p12042-12047, 6p |
| Abstrakt: |
We present the analysis of the evolution of tumors in a case of hepatocellular carcinoma. This case is particularly informative about cancer growth dynamics and the underlying driving mutations. We sampled nine different sections from three tumors and seven more sections from the adjacent nontumor tissues. Selected sections were subjected to exon as well as whole-genome sequencing. Putative somatic mutations were then individually validated across all 9 tumor and 7 nontumor sections. Among the mutations validated, 24 were amino acid changes; in addition, 22 large indels/copy number variants (>1 Mb) were detected. These somatic mutations define four evolutionary lineages among tumor cells. Separate evolution and expansion of these lineages were recent and rapid, each apparently having only one lineage-specific protein-coding mutation. Hence, by using a cell-population genetic definition, this approach identified three coding changes (CCNG1, P62, and an indel/fusion gene) as tumor driver mutations. These three mutations, affecting cell cycle control and apoptosis, are functionally distinct from mutations that accumulated earlier, many of which are involved in inflammation/immunity or cell anchoring. These distinct functions of mutations at different stages may reflect the genetic interactions underlying tumor growth. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
