Scientists Crack 'Entire Genetic Code' of Cancer

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."

Comments

Re:Sadly, the article makes no sense

[ColdWetDog]

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.

The extrapolation for lung cancer is badly flawed

[WhiskerBiscuit]

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.

Re:Sadly, the article makes no sense

[izomiac]

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).

Tell That to Monsanto

[Telephone Sanitizer]

> 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

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

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."

Re:Sadly, the article makes no sense

[RDW]

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.