The three genes are located next to each other on human chromosome 14 and two are known to play key roles in fetal lung development. According to CSHL lead investigator David Mu, lung cancer cells in adults can reactivate genes that are normally active in the earliest stages of lung development. We identified the mutation that triggers this abnormal re-activation of developmental genes and showed that if you turn off these genes, you stop the cancer.

The CSHL research found that the three genes termed TTF1, NKX2-8, and PAX9 interact to reactivate what appears to be an early fetal gene expression pattern that results in cancer tumor growth. The collaboration of these genes and the fact that they are so close together on the chromosome may explain why this mutation is so common in lung cancer, said CSHL investigator and co-author Scott Powers. In collaboration with Dr. William Gerald at the Memorial Sloan Kettering Cancer Center, the study finds that the mutation is more prevalent in late stage lung cancer and is possibly a risk factor for recurrence.

The CSHL-led research demonstrates that the cancerous results of the mutation can be reversed. In the future, this may lead to new treatment options for patients. Cancer research that looks at one gene at a time ignores the fact that cancers are usually caused by multiple collaborating cancer genes. Mutations in these genes determine the clinical outcome of the cancerous growth and how the cancer responds to treatment.

At CSHL we are excited about the ability to apply direct genomic analysis to human cancers and discover more about how cancer genes interact, said Howard Hughes Medical Institute Investigator and CSHL Cancer Center Deputy Director Scott Lowe.

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''The fundamental techniques developed by Martin Evans and his fellow winners have allowed scientists to unravel how genes work in mammals. Together, they figured out how to remove one gene from a mouse at a time allowing us to study how the loss of a gene might disrupt diverse biological processes from development to the function of the brain. As mouse and human genomes are almost identical this approach is having an enormous impact on our understanding of human disease. The ability to study how individual genes might cause disease, leads to enormous opportunities for the development of new approaches to therapeutics and treatment.''

Gene targeting in mice has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come. 

The medicine prize was the first of the six 2007 Nobel awards to be announced. The other awards are for chemistry, physics, literature, peace and economics.

Winners of the The Nobel Prize in Physiology or Medicine for 2007

Sir Martin J. Evans, born 1941 in Great Britain, British citizen, PhD in Anatomy and Embryology 1969, University College, London, UK. Former Director of the School of Biosciences and Professor of Mammalian Genetics, Cardiff University, UK. Mario R. Capecchi, born 1937 in Italy, US citizen, PhD in Biophysics 1967, Harvard University, Cambridge, MA, USA. Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT, USA. Oliver Smithies, born 1925 in Great Britain, US citizen, PhD in Biochemistry 1951, Oxford University, UK. Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.

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