The Academy: April 2007

By Querida Anderson, Prachi Patel-Predd, and John D. Zoidis, MD
Published: Friday, Aug 13, 2010
%u25BA Wellcome Trust Sanger Institute

     Largest Cancer Genome Study Implicates More Mutations than Previously Thought

The broadest survey yet of cancer genomes suggests that the number of mutated genes that drive development of the disease is greater than previously thought. Along with the driver mutations, each cell type carries many more passenger mutations that have no consequence on cancer formation. The study thus implies that the challenge lies in the ability to siftthrough mutations and decipher the drivers from the passengers.

“The human genome is a vast place and this, our first deep systematic exploration in cancer, has thrown up many surprises,” noted Mike Stratton, co-leader of the Cancer Genome Project at the Sanger Institute.

Scientists at the Wellcome Trust Sanger Institute report in Nature that they sequenced more than 250 million letters of DNA code, covering more than 500 genes and 200 cancers. The team identified possible driver mutations in 120 genes, most of which had not been seen before.

“It turns out that most mutations in cancers are passengers,” explained Dr. Andy Futreal, also co-leader of the Cancer Genome Project. “However, buried amongst them are much larger numbers of driver mutations than was previously anticipated. This suggests that many more genes contribute to cancer development than was thought.”

To distinguishing between the driver and passenger mutations, scientists will have to analyze much larger numbers of each cancer type. Faster DNA sequencing technologies will be important to achieve the scale of study needed.

The genes surveyed were of the kinase type, and Dr. Futreal said that one finding was that a group of kinases involved in the Fibroblast Growth Factor Receptor signaling pathway was hit much more than expected, particularly in colorectal cancers.

“This is a beautiful study,” commented Victor Velculescu, director of Cancer Genetics, from the Ludwig Center for Cancer Genetics and Therapeutics and Johns Hopkins University Kimmel Cancer Center. “It nicely shows the power of unbiased large-scale mutational analyses in human cancer and points to a large number of unappreciated protein kinases that appear to be important in tumorigenesis.”

The team also found that the mutations carry coded messages within them. The type of mutation varies between individual cancers, reflecting the processes that generated the mutations, some of which were active decades before the cancer showed itself. Although some patterns are understood, such as the signatures of damage from UV radiation or cancer-causing chemicals in tobacco, others still require decoding.

“The time is right to apply the powerful tools of genomics to obtain a comprehensive view of what goes wrong at the DNA level in cancer,” remarked Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute at the NIH.

                                                                                                                                                                                                 – Querida Anderson

%u25BA Memorial Sloan-Kettering Cancer Center

     Death Rates for Smokers Are Not Improved Although CT Screening Increases Early Diagnosis

Although CT screening found nearly three times as many lung cancers as predicted, researchers found no corresponding decrease in specifically detecting advanced lung cancers or in deaths from the disease.

The multicenter study was led by researchers at Memorial Sloan-Kettering Cancer Center, who published their findings in the March 7 issue of the Journal of  the American Medical Association.

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