A 1.4-Mb High-Resolution Physical Map and Contig of Chromosome Segment 11p15.5 and Genes in the LOH11A Metastasis Suppressor Region |
| |
| Affiliation: | 1. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;2. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA;3. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA;4. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA;5. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;6. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA;7. JHDSF Program, Harvard University, Cambridge, MA 02138, USA;8. FAS Division of Science, Harvard University, Cambridge, MA 02138, USA;9. Center for Advanced Imaging, Harvard University, Cambridge, MA 02138, USA;10. Spectroscopy Department, Physics Division, National Research Centre, Dokki, 12622 Cairo, Egypt;11. Department of Physics, University of Illinois at Chicago, Chicago, IL 60607, USA;12. Biology Department, University of Massachusetts, Amherst, Amherst, MA 01003, USA;1. Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA;1. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA;1. Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan;2. Department of Genetics, School of Life Science, Sokendai (Graduate University for Advanced Studies), Mishima, Shizuoka 411-8540, Japan |
| |
| Abstract: | The centromeric part of chromosome segment 11p15.5 contains a region of frequent allele loss in many adult solid malignancies. This region, called LOH11A, is lost in 75% of lung cancers and is thought to contain a gene that may function as a metastasis suppressor. Genetic complementation studies have shown suppression of the malignant phenotype including reduction of metastasis formation. We constructed a high-resolution physical map and contig over 1.4 Mb that includes the β-hemoglobin gene cluster and the gene for the large subunit of ribonucleotide reductase (RRM1). Through sequencing and computerized analysis, we determined that this region contains an unusually large number of transposable elements, which suggests that double-stranded DNA breaks occur frequently here. Twenty-two putative genes were identified. Because of its location at the site of maximal allele loss in the 650-kb LOH11A region and previous functional studies, RRM1 is the most likely candidate gene with metastasis suppressor function. The malignant phenotype, in this case, results from a relative loss of function rather than a complete loss. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
