トランスポゾンを使ってマウスに発癌させちゃうぞ

サイエンス一昨日のオンライン論文から
Published Online February 26, 2009
mutagenic Sleeping Beauty (SB) transposons なる道具を使ってマウスの腸管に発癌させる実験系である。

これでAPC, PTEN and SMAD4などが、やはり発癌経路に乗るとすれば面白い。マウスとヒトで同じかという問題が解決される。本文を読んでいないが、これはVogelsteinグループのWoodの論文を強く意識した研究だろうが（なぜならdriverやpassengerという言葉が出てくる）、単一腫瘍にどれだけの変異が蓄積されているのか、Woodらが言うように70前後はたまるのかどうかが知りたい。重要なことであるが「転移」は変異で説明できるのかどうか・・・答えがこの論文の中に書いてあるとすれば素晴らしい。

面白そうな論文であり、一日も早く読みたい。
Submitted on July 10, 2008
Accepted on February 6, 2009

A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer

Timothy K. Starr 1*, Raha Allaei 1, Kevin A. T. Silverstein 2, Rodney A. Staggs 2, Aaron L. Sarver 2, Tracy L. Bergemann 3, Mihir Gupta 4, M. Gerard O’Sullivan 5, Ilze Matise 5, Adam J. Dupuy 6, Lara S. Collier 7, Scott Powers 8, Ann L. Oberg 9, Yan W. Asmann 9, Stephen N. Thibodeau 9, Lino Tessarollo 10, Neal G. Copeland 11, Nancy A. Jenkins 11, Robert T. Cormier 12, David A. Largaespada 1*

1 Department of Genetics, Cell Biology and Development, Arnold & Mabel Beckman Center for Transposon Research, the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
2 Biostatistics and Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
3 Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
4 Harvard University, Cambridge, MA.
5 College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
6 Anatomy and Cell Biology, University of Iowa, Iowa City, IA, 52242, USA.
7 School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
8 Cold Spring Harbors Laboratory, Cold Spring Harbor, NY 11724, USA.
9 Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
10 Neural Development Group, Mouse Cancer Genetics program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
11 Institute of Molecular and Cell Biology, Singapore, 138673.
12 University of Minnesota Medical School, Duluth, MN 55812, USA.


Human colorectal cancers (CRCs) display a large number of genetic and epigenetic alterations, some of which are causally involved in tumorigenesis (drivers) and others that have little functional impact (passengers). To help distinguish between these two classes of alterations, we used a transposon-based genetic screen in mice to identify candidate genes for CRC. Mice harboring mutagenic Sleeping Beauty (SB) transposons were crossed to mice expressing SB transposase in gastrointestinal tract epithelium. Most of the offspring developed intestinal lesions including intraepithelial neoplasia, adenomas, and adenocarcinomas. Analysis of over 16,000 transposon insertions identified 77 candidate CRC genes, 60 of which are mutated and/or dysregulated in human CRC and thus are most likely to drive tumorigenesis. These genes include APC, PTEN and SMAD4. The screen also identified 17 new candidate genes that had not previously been implicated in CRC, including POLI, PTPRK, and RSPO2.