Title |
A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, May 2012
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DOI | 10.1073/pnas.1206062109 |
Pubmed ID | |
Authors |
Wen Xue, Thomas Kitzing, Stephanie Roessler, Johannes Zuber, Alexander Krasnitz, Nikolaus Schultz, Kate Revill, Susann Weissmueller, Amy R. Rappaport, Janelle Simon, Jack Zhang, Weijun Luo, James Hicks, Lars Zender, Xin Wei Wang, Scott Powers, Michael Wigler, Scott W. Lowe |
Abstract |
The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanism in the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 3 | 75% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 50% |
Scientists | 2 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 3% |
Spain | 2 | 1% |
Canada | 1 | <1% |
Brazil | 1 | <1% |
Unknown | 143 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 43 | 28% |
Researcher | 34 | 23% |
Student > Master | 12 | 8% |
Professor > Associate Professor | 9 | 6% |
Student > Bachelor | 9 | 6% |
Other | 27 | 18% |
Unknown | 17 | 11% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 65 | 43% |
Biochemistry, Genetics and Molecular Biology | 37 | 25% |
Medicine and Dentistry | 18 | 12% |
Computer Science | 4 | 3% |
Mathematics | 2 | 1% |
Other | 5 | 3% |
Unknown | 20 | 13% |