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Medicine

Scientists Crack 'Entire Genetic Code' of Cancer 235

Posted by samzenpus
from the whole-tumor dept.
Entropy98 writes "Scientists have unlocked the entire genetic code of skin and lung cancer. From the article: 'Not only will the cancer maps pave the way for blood tests to spot tumors far earlier, they will also yield new drug targets, say the Wellcome Trust team. The scientists found the DNA code for a skin cancer called melanoma contained more than 30,000 errors almost entirely caused by too much sun exposure. The lung cancer DNA code had more than 23,000 errors largely triggered by cigarette smoke exposure. From this, the experts estimate a typical smoker acquires one new mutation for every 15 cigarettes they smoke. Although many of these mutations will be harmless, some will trigger cancer.' Yet another step towards curing cancer. Though it will probably take many years to study so many mutations."
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Scientists Crack 'Entire Genetic Code' of Cancer

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  • by ColdWetDog (752185) on Wednesday December 16, 2009 @08:36PM (#30467118) Homepage

    Is it that the one melanoma they looked at had 30,000 differences from the other cells in the patient's body? It appears that, far from finding the needle in the haystack, they've found 30,000 haystacks.

    Not quite. It's more like they ** think ** they've found a map to the 30,000 needles in a single haystack and they hope that the haystacks (individual humans) are similar enough that they can generalize a bit on how to find the other needles in other haystacks.

    FTFAbstract:

    All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.

    The researchers state (and I haven't really had time to look at the article) that they have identified all, or at least the vast majority, of mutations from a single cancer and furthermore have managed to characterize (see above) the mutations. Other researchers have done similar research for other cancers. The idea is that, after all of this information is digested, somebody can use this knowledge to figure out better treatments for cancers. Of course, this remains to be seen. It's reasonable but by no means certain. The babble at the end of the BBC article is typical hyperbole.

  • Misleading... (Score:1, Informative)

    by Anonymous Coward on Wednesday December 16, 2009 @08:37PM (#30467134)

    This is a terrible summary. There is no *single* cancer genome. They sequenced the genome of one cancer biopsy. There are probably as many different cancer "codes" (also a horribly misleading term) as there are tumors in the world.

    Cancer is not a single disease, it is a phenomenon, like evolution. This would be like sequencing the genome of two organisms and claiming to've "cracked the evolution code".

  • by WhiskerBiscuit (811421) on Wednesday December 16, 2009 @08:45PM (#30467216) Homepage
    Cancer cells start accumulating mutations as a consequence of rapid cell division and poor quality control on DNA replication; they also have problems keeping their chromosomes intact. This is called "genomic instability" and it is a hallmark of cancer.

    The critical point here is that most of these mutations are acquired *after* the cancer gets going, regardless of whether the mutagen in question is still being administered.

    Therefore, it's not proper to infer a linear relationship between the dose of mutagen and the number of mutations.

    Beyond that, the numbers involved in that extrapolation seem to have been pulled out of thin air, and I question whether they knew the smoking history of the individual who donated the material that created that cell line. (The lung cancer in question had 30,000 mutations, so by their logic the smoker must have smoked 345,000 cigarettes, or 17,250 packs of 20. That's a pack a day for 47 years, which is admittedly within the bounds of possibility, but still an awful lot of smoking.)

    Whatever. Smoking is still awful for you, but this kind of nonsensical extrapolation without regard to detail is terribly annoying.

  • by scapermoya (769847) on Wednesday December 16, 2009 @09:18PM (#30467556) Homepage
    I just completed an intensive undergraduate course on cancer with a focus on genetics at UC Berkeley. We spent a significant amount of time on cancer genomes, and I have to say this announcement doesn't mean that much unfortunately. Cancers are genetically very unstable, and any given tumor you sequence will have many mutations that are completely unrelated to the cancer's survival and proliferation. they are known as passenger mutations, and need to be separated from the causative 'driver' mutations. sequencing many tumors of the same type and applying statistical analysis has been useful in this area, but considering that there are potentially millions of different combinations of active and inactive genes that lead to tumor formation, this approach has its limitations. this is especially true given that some genes are both tumor suppressors and tumor activators in different contexts (eg the TGF-b pathway). even if you identify a genetic locus as highly associated with a particular cancer, it is hard to go from there to understanding the molecular biology behind that association.

    we have a long way to go before we defeat cancer, and sequencing can only take us so far.
  • by izomiac (815208) on Wednesday December 16, 2009 @09:28PM (#30467634) Homepage
    That's pretty much on target. UV light is absorbed by DNA, and it causes changes like Thymine-Thymine dimers (ATCG are DNA bases, a T-T dimer is when two adjacent T's on the same strand bind to each other). Cells have DNA repair mechanisms, some of which are accurate, others of which are not. If the repair is inaccurate you have a mutation in a semi-random location (needs something like two adjacent thymines, and it probably needs to not be in it's condensed storage form). A mutation in each of about 8 genes that control the cell cycle will lead to uncontrolled replication and further mutation. Certain types of cells are vulnerable to different things, and require certain genes to be knocked out (or overexpressed) to form certain types of cancer. It's all very random, but there are trends within each type of cancer (hence its behavior).
  • by Telephone Sanitizer (989116) on Wednesday December 16, 2009 @09:49PM (#30467818)

    > The genes aren't patentable.

    Tell that to Monsanto. If the genes from their GE plants turn up in a farmer's soy crop, he's in for hell even if they just drifted over as pollen from neighboring fields.

    In the United States, patents protect not just the device or technique, but also the product of it. Thus, those who patent techniques for isolating genes also have patent-protection for the genes, themselves. Patents do not ordinarily cover "products of nature," but when something exists in a lab in "purified" form, it's exempted from this limitation. http://www.ornl.gov/sci/techresources/Human_Genome/elsi/patents.shtml [ornl.gov]

    Here's what Monsanto does with their patents:
    http://www.commondreams.org/headlines05/0115-04.htm [commondreams.org]

    Under U.S. patent law, a farmer commits an offense even if they unknowingly plant Monsanto's seeds without purchasing them from the company. Other countries have similar laws.

    In the well-known case of Canadian farmer Percy Schmeiser, pollen from a neighbor's GE canola fields and seeds that blew off trucks on their way to a processing plant ended up contaminating his fields with Monsanto's genetics.

    The trial court ruled that no matter how the GE plants got there, Schmeiser had infringed on Monsanto's legal rights when he harvested and sold his crop. After a six-year legal battle, Canada's Supreme Court ruled that while Schmeiser had technically infringed on Monsanto's patent, he did not have to pay any penalties.

    Schmeiser, who spoke at last year's World Social Forum in India, says it cost 400,000 dollars to defend himself.

    "Monsanto should held legally responsible for the contamination," he said.

    Another North Dakota farmer, Tom Wiley, explains the situation this way: "Farmers are being sued for having GMOs on their property that they did not buy, do not want, will not use and cannot sell."

  • by RDW (41497) on Wednesday December 16, 2009 @09:52PM (#30467862)

    It's true that each patient is extremely likely to have a unique 'cancer genome', a specific combination of mutations found only in their tumour. But the vast majority of these will be 'passenger' mutations that aren't relevant to the progress of the tumour. The trick, as you suggest, is to home in on the 'driver' mutations that are really causing the disease. One way to get at these is to look first at the mutations in the coding sequences of known genes (and because of the human genome project and all the work that's followed it, we pretty much know where all the protein-coding genes are located).

    I just had a quick look at both papers, and it turns out that in the lung cancer case, fewer than 100 of the tens of thousands of mutations actually cause an amino acid change in a protein sequence (for the melanoma, the figure is less than 200). This doesn't mean that there aren't other interesting needles to find in the haystack of mutations (e.g. changes in regulatory sequences), but they might as well go after the 'low hanging fruit' first. With current technology, it's very easy to sequence 100-200 genes in a pretty large set of samples from different patients. Any of these genes that turn out to be mutated in multiple tumours immediately become subjects for further study.

    As the technology starts to ramp up and gets cheaper every year, we can begin to go after the less obvious changes. Each of these studies is in effect an entire human genome project (they haven't just done a low resolution map, they've completely sequenced the genomes). Pretty soon we're going to have a large collection of sequenced tumour samples to compare and use to find common alterations.

  • by RDW (41497) on Wednesday December 16, 2009 @10:07PM (#30468008)

    In these particular studies, they're only looking at 'somatic mutations' (mutations confined to the tumour, and not found in the patient's normal cells). Anything they inherited that might have made them susceptible to cancer in the first place gets 'cancelled out' by comparing the tumour DNA to normal DNA (e.g. from blood). You have to do a different type of study to find susceptibility genes, e.g. by using a large collection of 'normal' DNA samples from a population and collecting their medical data. Right now, this is being done at a relatively low resolution using 'SNP arrays' that usually only look at a few hundred thousand DNA bases (a few million max). But because of genetic linkage, this can still give you very useful information about where the important genes are. When the genome sequencing technology gets _really_ cheap, we can except this sort of study to be done by sequencing too.

  • Re:How real is this? (Score:2, Informative)

    by amirulbahr (1216502) on Wednesday December 16, 2009 @10:23PM (#30468146)
    Not redundant. Seriously, think before you mod. You may not like the post but it's definitely not redundant as no one else has made the same comment.

    Try to mod good posts up, rather than look for ones you disagree with and mod down. If you must, then a -1 Flamebait or Overrated would be more appropriate here.

  • by RDW (41497) on Wednesday December 16, 2009 @10:28PM (#30468180)

    They started off with a couple of common cancers, but the plan is to do many more:

    http://www.sanger.ac.uk/about/press/2008/080429.html [sanger.ac.uk]

    'The ICGC will identify a list of approximately 50 cancer types and subtypes that are of clinical significance around the globe, aiming to study cancers of all major organs, including breast, ovary, prostate, lung and blood cancers...All the data generated will be made rapidly and freely available to the global research community. '

  • by RDW (41497) on Wednesday December 16, 2009 @10:37PM (#30468246)

    'Show me the evidence that almost 100% of DNA errors in skin cells or skin cancer cells are caused by sun exposure...'

    Not 100% perhaps, but from the paper:

    'DNA damage due to ultraviolet light leads to the formation of covalent links between two adjacent pyrimidines. Consequently, C>T mutations due to ultraviolet light usually occur at dipyrimidine sequences. Therefore, to evaluate further the role of ultraviolet light in the pathogenesis of somatic mutations in COLO-829, we examined the sequence context of C>T substitutions...[Lots of technical stuff about the sequence context of the mutations with some impressive looking p-values] ...Therefore, the mutation spectrum and sequence context indicate that most C>T/G>A somatic substitutions in COLO-829 are attributable to ultraviolet-light-induced DNA damage.'

  • by Valdrax (32670) on Wednesday December 16, 2009 @11:21PM (#30468546)

    This is why car drivers that complain about cigarette smokers annoy me. The will spew all sorts of particulate matter and chemicals into the air and then whine when a cigarette smokers do it. Yes, I drive, and no I don't smoke, but I'm not going to be a hypocrite and claim that my air pollution is better than their air pollution.

    It wouldn't necessarily be hypocrisy to claim that.

    1) Cigarette smoke contains 10x more particulate matter [medicalnewstoday.com] than engine exhaust. There's a reason we have catalytic converters.
    2) Cars don't typically blow smoke at face level or hang around doors (or indoors in more permissive places).

  • by Dr. Hellno (1159307) on Wednesday December 16, 2009 @11:33PM (#30468614)
    It's actually not well understood, or at least not well-proven, exactly what it is in cigarettes that causes cancer. Hilariously, everyone I know who smokes weed thinks there's a clear case to be made that weed is "better" because it doesn't have "chemicals". Of course, it's made ENTIRELY of chemicals, just like everything else.

    I read a few years ago that people who drink hot coffee have a higher incidence of throat cancer. Heat is a big factor here, and certain oxidized compounds are likely involved too, but it's not entirely obvious which ones.
  • by Telephone Sanitizer (989116) on Thursday December 17, 2009 @12:35AM (#30469088)

    I think you're deliberately misunderstanding a patented product produced by genetic manipulation so that you can introduce a completely unrelated topic.

    Genes are not patentable.

    Sequences of genes are patentable.
    http://en.wikipedia.org/wiki/Gene_patent [wikipedia.org]

    Many of the farmers sued by Monsanto have never used Monsanto seed and never had Monsanto seeds end up in their fields.

    Often, GE pollen crosses a few fields and contaminates neighboring farms. Monsanto's agents do (sometimes illegal) spot-checks and discover that a farmer's crop contains genes from the Monsanto seeds and then they sue to confiscate the entire crop or to force the farmer to incinerate his fields as an infringer.

    It is not the presence of the original product (the Monsanto seeds) that they sue over. It is the presence of sequences of genes that they own the rights to. If the only thing that they had rights to were the original seeds then they would have no standing to sue over hybrids from pollen from their seeds.

    The situation is getting worse as time goes on and courts get involved more often. When they sue, they try to cover as many broad arguments as they can. Companies patenting sequences of RNA are now even claiming rights over the proteins and DNA that the RNA codes for. As they usually sue poor agrarians who can't afford to put up a good defense, bad judgments are becoming strong precedents.

    Look up "product by process" for more info.

    Here's a start for you:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2220018/ [nih.gov]

    Patents on human genetic compositions of matter cover a broad array of chemicals and technologies. For example, human insulin, human growth hormone and many other proteins that can be isolated and purified from human blood or urine can be patented. Further, synthesized products can be covered by various patent claims, including (1) claims to the sequences used (both the sequence to be transcribed into RNA and proteins as well as promoter sequences); (2) the virus or other vectors containing the claimed sequence; (3) transfected cells, cell lines and nonhuman organisms created and used in these processes, and, perhaps most importantly, (4) the proteins or other therapeutic products made by these claimed processes. The last, called 'product by process' claims, allow patent owners to prohibit the use or sale of products made by the claimed processes, regardless of where the product is made.

  • by Anonymous Coward on Thursday December 17, 2009 @12:55AM (#30469242)

    Nope. There's been a large reduction in cancer deaths due to research and treatment advances

    Unfortunately, that's not really true - the overall mortality rate [nytimes.com] for cancers is roughly the same as it was in 1950, as aresurvival rates for people diagnosed with cancer. [lww.com]

    I would suggest that spending more money on cancer research is unlikely to have a significant impact on survival rates. From the proteins on his surface to the sequence of his DNA, we know the enemy. What we lack is the bullet that can reach him and kill him - essentially the same problem that prevents us from curing AIDS, antibiotic-resistant bacteria, and many genetic diseases. Now that gene therapy has proven to be a dud, there's no incremental advancement on the horizon that could lead to a large increase in cancer survival rates. Funding is unlikely to help because the advisory boards making the money decisions prioritize incremental research [nytimes.com] deemed most likely to succeed over more ambitious experiments. The few major breakthroughs in treating specialized forms of cancer have mostly come from lone wolves [wikipedia.org] who secured funding from private benefactors.

    No one can argue against funding cancer research while so much of our economic output is earmarked for empire building or making really great sitcoms. But I do not believe that additional funding for cancer research is likely to produce a large increase survival rates.

  • by wirelessbuzzers (552513) on Thursday December 17, 2009 @04:00AM (#30470530)

    It costs on the order of $10k to sequence a single genome. But you wouldn't do it for every cancer patient. Instead, you'd do it for a couple hundred cancer patients, and study the results. You'd hope to find a few dozen common mutations which indicate which treatment to use. Checking a cancer for a few dozen known marker genes is considerably easier than sequencing an entire genome.

  • by Hrshgn (595514) <rince2001&gmx,ch> on Thursday December 17, 2009 @06:48AM (#30471564)
    Nature has a nice summary of the original research paper published in the same journal: http://www.nature.com/news/2009/091216/full/news.2009.1143.html [nature.com]

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