Cancer genomes sequenced

Scientists have charted the most complete cancer genomes to date, according to two studies published in Nature this week, providing a catalog of some 90% of all the somatic mutations in melanoma and a type of lung cancer, as well as a starting point for identifying potentially causal mutations common to these types of cancer. Cross section of a human lung with cancerImage: Wikimedia commons"For the first time we have a really quite comprehensive view of two different common tumor types," said l

By | December 16, 2009

Scientists have charted the most complete cancer genomes to date, according to two studies published in Nature this week, providing a catalog of some 90% of all the somatic mutations in melanoma and a type of lung cancer, as well as a starting point for identifying potentially causal mutations common to these types of cancer.
Cross section of a human lung with cancer
Image: Wikimedia commons
"For the first time we have a really quite comprehensive view of two different common tumor types," said linkurl:Bert Vogelstein;http://www.hopkinsmedicine.org/pharmacology/research/vogelstein.html of Johns Hopkins Medicine, who was not involved in the research. "That information will form the foundation for subsequent studies." Previously, scientists studying cancer genomes had identified a handful of so-called driver mutations -- those that have a causative effect on the cancerous growth. But these two papers are the first to also analyze the noncoding regions of the genome, which may also contain driver mutations that could act by altering gene expression, Vogelstein said. Using shotgun sequencing techniques, linkurl:Michael Stratton;http://www.icr.ac.uk/research/research_profiles/2750.shtml of the Wellcome Trust Sanger Institute and the Institute of Cancer Research in the UK and his colleagues compiled a list of more than 50,000 somatic mutations in a small-cell lung cancer metastasis and a malignant melanoma cell line. Comparing them to known mutations in these cancer types, the researchers determined they had identified approximately 90% of all the mutations in the cancer cell lines, Stratton said. Finally, using traditional PCR techniques to search the genomes for newly identified mutations, the shotgun sequencing appeared to result in only about a 3% false positive rate. "That's a high quality catalog," Stratton said. From these catalogs, the researchers further identified the types of mutations that were most prominent in each cancer type and found them to be consistent with their known causes of ultraviolet light and tobacco carcinogens. The lung cancer genome, for example, was riddled with G to T substitutions, while the melanoma cell line carried predominately C to T mutations. linkurl:Gerd Pfeifer,;http://www.cityofhope.org/directory/people/pfeifer-gerd/Pages/default.aspx a molecular biologist at the City of Hope clinical research hospital in California, found the similarity among the mutation types within a particular cancer genome "quite surprising." While scientists had previously identified a handful of mutations found in these particular cancer types, "people thought that was maybe a unique situation," said Pfeifer, who was not involved in the research. "But it seems to be a much more general phenomenon that affects the entire genome." Thus, by knowing the complete genomes of a variety of cancer types, Pfeifer added, "we might understand [something] about the etiology of these cancers." For melanoma and lung cancer, scientists have a pretty good understanding of what causes the mutations, but for many other cancer types, such as breast or pancreatic cancer, the "mutational signatures" revealed by these types of sequencing studies may get scientists "closer to understanding the origin of the tumors," he said. "I think over the next year you can be absolutely confident there will be dozens if not hundreds of different tumors looked at," Vogelstein said. In addition to sequencing more different kinds of cancers, there will be a "profound benefit" of sequencing more cell lines from the same tumor type, said Stratton. By identifying mutations that show up consistently in hundreds of different tumors of the same type, he said, scientists will be able to pinpoint additional driver mutations of specific cancers. These genes may present new drug targets for cancer therapies. A complete list of the driver mutations in any particular cancer type can then serve as the ultimate diagnostic tool, Stratton added. Looking at a particular tumor in a particular patient and being able to identify which driver mutations it carries "will give us a good indication of which drugs the patient will respond to," he said, "[giving] us a much more refined way of applying cancer therapy to the benefit of patients." "This is a landmark moment in cancer research," Stratton said. "From this moment on, this is going to be our expectation for what we want to know about individual cancers -- it resets our ambitions for cancer."
**__Related stories:__***linkurl:Cancer research, stimulated;http://www.the-scientist.com/blog/display/55649/
[21st April 2009]*linkurl:More than 150 new cancer mutations found;http://www.the-scientist.com/news/home/52929/
[7th March 2007]*linkurl:Developing the Ideal Breast Cancer Screening Test;http://www.the-scientist.com/article/display/12492/
[9th July 2001]
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Comments

Avatar of: Christopher Lee

Christopher Lee

Posts: 50

December 16, 2009

I hope you will be able to provide in due course a more detailed article on this important subject.
Avatar of: Camilo Colaco

Camilo Colaco

Posts: 10

December 17, 2009

Still at a loss to understand how yet further confirmation of the genetic individuality of a patient's cancer will advance treatment? Is the proposal to sequence each patient's DNA to identify tumourgenic mutations and design individual treatments based on the molecular genetic defects?\n\nCC\nPS would patient specific immunotherapy qualify as personalised medicine?

December 17, 2009

Quote: "That information will form the foundation for subsequent studies."\n\nWhat if the foundation is shaky? Every person who worked with cell lines a bit more knows that cell lines do not resemble too much the situation in the donor some (tens of) years ago, when the sample was prelevated. You end up even having chromosomal rearrangements, not to mention other, more minor but often changes in the genetic material.\n\nWhy not sequence fresh sample from a patient? Do we try to understand cancerous cell lines, or cancer occuring in actual patients?
Avatar of: Jeff Wine

Jeff Wine

Posts: 2

December 19, 2009

Thank you for calling attention to this research. Would it be possible to include a direct link to articles being discussed? Many readers of the Scientist are likely to have access rights to journals in which top research appears. (Apologies if a link is present and I missed it.)
Avatar of: Alison McCook

Alison McCook

Posts: 68

December 20, 2009

Here's a link to the paper. \n\nhttp://www.nature.com/nature/journal/vaop/ncurrent/full/nature08658.html\n\nAlison McCook\nDeputy Editor
Avatar of: anonymous poster

anonymous poster

Posts: 1

February 1, 2010

As above, your article mentioned Two papers, could you please provide the 2nd link to the other paper? Many thanks.
Avatar of: Jef Akst

Jef Akst

Posts: 28

February 1, 2010

Here you go: http://www.nature.com/nature/journal/v463/n7278/full/nature08629.html

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