Genome-wide scan maps mutations in deadly lung cancers; reveals embryonic gene link
Scientists have completed a comprehensive map of genetic mutations linked to an aggressive and lethal type of lung cancer.
Among the errors found in small cell lung cancers, the team of scientists, including those at the Johns Hopkins Kimmel Cancer Center, found an alteration in a gene called SOX2 associated with early embryonic development.
"Small cell lung cancers are very aggressive. Most are found late, when the cancer has spread and typical survival is less than a year after diagnosis," says Charles Rudin, M.D., Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center. "Our genomic studies may help identify genetic pathways responsible for the disease and give us new ideas on developing drugs to treat it."
The scientists found an increase in the copy number of the SOX2 gene in about 27 percent of small cell lung cancer samples. The resulting overproduction of proteins made by the SOX2 gene may play a role in igniting or sustaining abnormal cell growth in the lung. SOX2 offers a new target for scientists working to develop new drugs to combat this intractable cancer, say the investigators.
For the study, published online Sept. 2 in Nature Genetics, colleagues from Johns Hopkins, Genentech, the University of Texas Southwestern Medical Center and the University of Colorado Cancer Center scanned the genome's coding regions of 63 small cell lung cancers, including 42 with matching samples from patients' normal cells.
The scientific team scanned 56 of the samples for evidence of "amplification," a cellular process seen in cancer in which cancer cells acquire more than the typical two gene copies inherited from each parent. They found that one of the genes, SOX2, was amplified, in about 27 percent of the samples (15 of 56). SOX2 encodes a protein complex that binds to DNA and controls when and how genes are decoded to make other proteins. It has been linked to tissue and organ development in embryonic cells, and is one of the four genes used by scientists to convert adult cells into an embryonic state.
The scientists confirmed SOX2 amplification in an independent set of 110 small cell lung cancers. This amplification, they found, causes cells to overproduce SOX2 proteins and may promote growth that leads to cancer. Samples with amplified SOX2 also correlated with patients who had more advanced disease. "SOX2 is an important clue in finding new ways to treat small cell lung cancer," says Rudin. "We may be able to link a patient's outcome to this gene and develop a drug to target it or other genes it regulates." Rudin says his team will further explore the function of SOX2 and how to target it.
In addition to amplification, the study mapped errors in the genome's sequence and protein production levels.
In a second report appearing in the Sept. 2 issue of Nature Genetics, scientists from Germany and elsewhere completed another genome wide scan of small cell lung cancers and focused on changes in several genes, including FGFR1, a growth factor previously linked to cancer development. Rudin says FGFR1 may prove to be a rare but significant change among small cell lung cancers.
More information: Nature Genetics paper: www.nature.com/ng/… ng.2405.html
Journal reference: Nature Genetics
Provided by Johns Hopkins University School of Medicine
- Japanese scientists explore pluripotency May 23, 2007 | not rated yet | 0
- Expression of pluripotency-associated gene marks many types of adult stem cells Oct 06, 2011 | not rated yet | 0
- KRAS gene mutation and amplification status affects sensitivity to antifolate therapy Apr 04, 2012 | not rated yet | 0
- What decides neural stem cell fate? May 05, 2011 | not rated yet | 0
- Protein KO stops tumour growth Apr 19, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Genetics 8 hours ago | not rated yet | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
8 hours ago | 4.7 / 5 (3) | 0 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
5 hours ago | 5 / 5 (1) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
5 hours ago | 5 / 5 (1) | 2 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
6 hours ago | not rated yet | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
7 hours ago | 5 / 5 (1) | 0 |
(HealthDay)—Implementation of systematic monitoring for medication adherence will allow for identification of barriers to adherence and tailoring of interventions, according to a viewpoint piece published ...
4 hours ago | not rated yet | 0