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Genetic parallels found between lung development and lung cancer

For over 100 years, biologists have speculated that cancer growth shares common features with embryonic development. Researchers at Children's Hospital Boston now provide solid evidence for this idea, showing through gene-chip analyses and bioinformatics techniques that many genes that are differentially expressed (turned "up" or "down") during early embryonic lung development are also differentially expressed in lung cancer.

More importantly, they show that gene-expression profiling can predict a lung cancer's prognosis, and that cancers whose gene expression pattern resembles gene expression during the earliest stages of lung development have the worst prognosis of all.

"This confirms our earlier finding of the importance of normal organ development in understanding cancer," says Isaac Kohane, MD, PhD, director of the CHIP program and a co-author on the paper. "Our observations might translate into more accurate prognoses and help us identify mechanisms of cancer growth that can be therapeutically targeted."

Lung cancer, the world's leading cause of cancer deaths, has many known subtypes, but it is commonly misclassified, delaying appropriate treatment. In addition, cancers within a subtype may vary in their aggressiveness.

Seeking a better way to classify lung cancers, Hongye Liu, PhD, and colleagues in the Children's Hospital Informatics Program (CHIP) examined gene activity in tumors from 186 patients and compared it with the gene activity that occurs during normal embryonic lung development in mice. They also examined 17 samples of normal lung tissue. Starting with 3,500 genes known to be common to mice and humans, they identified 596 genes whose activity was altered both in lung tumors and during lung development.

Using the natural trajectory of lung development as a framework, Liu and colleagues were able to predict survival in patients with adenocarcinoma (the most common type of lung cance
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Contact: James Newton
james.newton@childrens.harvard.edu
617-355-6420
Children's Hospital Boston
3-Jul-2006


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