Milestone study probes cancer origin

BBC ^ | 2013 August 14 | James Gallagher

[CutePuppy]

Scientists are reporting a significant milestone for cancer research after charting 21 major mutations behind the vast majority of tumours.

The disruptive changes to the genetic code, reported in Nature, accounted for 97% of the 30 most common cancers.

Finding out what causes the mutations could lead to new treatments. Some causes, such as smoking are known, but more than half are still a mystery.

Cancer Research UK said it was a fascinating and important study.

A tumour starts when one of the building blocks of bodies, a cell, goes wrong. Over the course of a lifetime cells pick up an array of mutations which can eventually transform them into deadly tumours which grow uncontrollably.

Cancer origins.

The international team of researchers was looking for the causes of those mutations as part of the largest-ever analysis of cancer genomes.

The well-known ones such as UV damage and smoking mutate the DNA, increasing the odds of cancer.

But each also leaves behind a unique hallmark - a piece of "genetic graffiti" - that shows if smoking or UV radiation has mutated the DNA.

Researchers ... hunted for more examples of "graffiti" in 7,042 samples taken from the 30 most common cancers.

The found that 21 separate "graffiti signatures" could account for 97% of the mutations which led to cancer.

Prof Sir Mike Stratton, the director of the Sanger Institute, told the BBC: "I'm very excited. Hidden within the cancer genome are these patterns, these signatures, which tell us what is actually causing cancer in the first place - that's a major insight to have. ..... < snip >

..... "The genetic fingerprints ... identify several new processes driving the development of cancer ..... < snip >

[CutePuppy]

Big Data pattern recognition analysis may significantly speed up and potentially provide early diagnostics and methods of cancer treatments or prevention that are gentle on the system. Also this may avoid a number of false starts and trials that work on mice but not in human trials due to differences in the DNA.

Possibly related: Remnants of Ancient Viruses in Human Genome May Play Role in Cancer - SN, 2013 August 14

According to an international team of scientists from the United States, Europe and Russia, non-coding parts of the human genome known as vlincRNAs triggered by ancient viruses participate in the development of cancer.

They also found that the elimination of these vlincRNAs (very long intergenic, non-coding RNAs) caused the death of cancer cells. ..... < snip >

..... "Future research into the role and function of vlincRNAs holds promise for both highly targeted diagnostic tests and more precise cancer treatments.

Up to 98 percent of human genomic matter is known as ‘junk' non-coding DNA, and had for years attracted little interest among scientists who doubted its role in human health and disease.

Recent research has begun to identify that part of that non-coding DNA is used by the cell to make RNA such as vlincRNA, highly tissue-specific RNA chains of unusually large lengths, many of which are only found in embryonic or cancerous cells. ..... < snip >

Maybe, "junk DNA" is not all "junk"? If just 1% more is not junk, it increases "non-junk DNA" by 50% - quite a lot for useful research. The discovery of vlincRNA may also explain why embryonic stem cells have not been nearly as useful as adult stem cells in research and developing treatments.

Picture provided in the article is unenlightening, so not displayed here, to save the bandwidth.

[CutePuppy]

In case you might be interested:

"Hidden within the cancer genome are these patterns, these signatures, which tell us what is actually causing cancer in the first place - that's a major insight to have."

[exDemMom]

Some causes, such as smoking are known, but more than half are still a mystery.

We have here an example of why I dislike reading science written for the lay person.

DNA mutates randomly. We have several DNA repair enzymes, which do a pretty good--but not perfect--job of fixing the random mutations. Some things, like high doses of radiation, certain chemicals, or UV light, cause a higher than random rate of mutation. This higher than random rate can overwhelm the repair enzymes, causing a mutation to be "fixed" into the genome. The inaccuracy in this report is that, since there is *always* a chance that a spontaneous and random mutation will be "fixed" in the genome, this process really is not a mystery.

We have thousands of viruses residing in our genome. In some cases, viral DNA (there is no RNA in the genome) is necessary for life. A gene that all mammals use to form the placenta comes from a virus.

[CutePuppy]

We have here an example of why I dislike reading science written for the lay person.

"Lost in translation" for lay person :-)

I think what author tried to do is "classify" the signatures "related" to different potential causes that could affect immune system in some people, to make it more susceptible to a mutation getting "fixed". Later in the article:

Mysteries

Other signatures were related to ageing and the body's immune system. Cells respond to viral infection by activating a class of enzymes which mutate the viruses until they can no longer function.

[wideminded]

Finding out what causes the mutations could lead to new treatments. Some causes, such as smoking are known, There used to be a group of people on FR who liked to spread the idea that smoking is not really all that bad for you and the proclaimed dangers of smoking are just a bunch of propaganda. I have sometimes wondered how these people have been doing.

[SunkenCiv]

That second one could make a nice standalone topic, thanks CP.

[who_would_fardels_bear]

In other news, there are only 21 reasons that account for 97% of traffic accidents, only 21 reasons that account for 97% of suicides, only 21 reasons that account for 97% of heart attacks, only 21 reasons that account for 97% of new diabetes cases, etc.

[CutePuppy]

See Pareto Principle (aka 80/20 Rule, Golden Rule, the Law of Vital Few, etc.), i.e. variations of 20% of "input" are responsible for 80% of "output".

[CutePuppy]

Yes, it may have a different / separate subplot. Feel free to post it.

[nightlight7]

There used to be a group of people on FR who liked to spread the idea that smoking is not really all that bad for you and the proclaimed dangers of smoking are just a bunch of propaganda.

Thanks for your concern. I am doing just fine at 2-2.5 packs a day (non-filtered) for over 3 decades, despite having not visited docs since 1991 (or maybe because of that). These are some of my discussions on the subject on FR: thread1, thread2, thread3, thread4 (omitting few).

There was also a more recent debate (with some of new research data I found since then), at the nootropic & life-extension forum here (the second half of the post has TOC for the discussion highlights). As always, there was no contest -- all the hard science (experiment, lab analysis) was on my side, while poor antismoking hysterics could only find soft/junk science (see items #8, #15, #16 in the above TOC for explanation of the difference).

The more one learns what real science (in contrast to second hand and third hand retelling) actually discovered about this ancient medicinal plant, the better it looks. Any time some new biochemical lever of longevity is discovered (usually hailed as the latest 'fountain of youth' in the press), the literature search uncovers that the tobacco smoke, if it has any effect on it, it pushes the same lever in the right direction.

[sun7]

The inaccuracy in this report is that, since there is *always* a chance that a spontaneous and random mutation will be "fixed" in the genome, this process really is not a mystery.

The article clearly says the mysteries are what caused the mutations that led to cancer, not how or why mutations occur. It may be your opinion that all cancers are caused by spontaneous and random mutations; but that is not the premise of the article, hence no inaccuracy there. Besides, there are plenty of cancer patients young and old without any known or significant exposure to any of the risk factors you cited. How is cancer not still a mystery?!

We have thousands of viruses residing in our genome. In some cases, viral DNA (there is no RNA in the genome) is necessary for life. A gene that all mammals use to form the placenta comes from a virus.

And what does this entire paragraph have to do with the topic at hand?

Apparently, people have different likes and dislikes. I personally much prefer reading about science written for the lay person, than reading from lay persons eager to show off their knowledge after reading about something off the Internet or elsewhere.

[sun7]

Thanks for pinging. Yes, I am interested simply because I believe cancer will one day be curable.

I hope they will find something useful at the end of this study; but cancer has stricken such diverse groups of people across all age ranges that I’m not optimistic they can pinpoint exactly the things that definitively cause cancer.

I once read from a reliable source that [all] cancer is viral. The immune system therefore plays a decisive role in determining if a person will get cancer. I think that explains why some heavy smokers are fine while non-smokers come down with lung cancer. And, incidentally, a large % of melanoma are found on skin never exposed to the sun; so much about UV from the sun causing cancer.

Instead of trying to track down the apparently very elusive cause(s), which we have had little success after all these years, it seems the more promising approach is to try to find some common physiological or metabolic properties among cancer cells, and then to target them specifically; like what you posted earlier about the findings on the protein CPTP.

Even with our advances in technology and research capabilities, we definitely can use some serendipity to make a breakthrough like in the old days.

[sun7]

Wow, speak of the ..

Did you just happen to stumble onto this thread?

[nightlight7]

Did you just happen to stumble onto this thread?

Medicinal topics are usually interesting. The thread was short enough that I spotted the post on smoking which seemingly was referring to my previous discussions here, and I couldn't resists.

[Drango]

There used to be a group of people on FR who liked to spread the idea that smoking is not really all that bad for you and the proclaimed dangers of smoking are just a bunch of propaganda.

They are still here. Worse they dispute the scientific evidence that smoking puts a fetus at risk. Sick individuals trying to justify their own addiction, by ignoring/downgrading the risk to the unborn.

[CutePuppy]

I hope they will find something useful at the end of this study; but cancer has stricken such diverse groups of people across all age ranges...

That's exactly the point of such a large and broad study - to find commonalities based on the pattern of cancer signatures, rather than the ones we are paying attention to at this time (e.g., age, ethnicity, environment, exposure, diet, habits, genetics etc.) - it may point us in the right direction and allow much earlier diagnostics and better screening for potentially effected individuals based on DNA signatures (genetically predisposed from birth or due to "fixed" mutation) rather than grouping by broad "medieval" observational / statistical categories of "smoker," "red meat eater," "suntan/UV" etc.

I once read from a reliable source that [all] cancer is viral.

Actually, unless you mean the viral mutation of genome, externally "the cause" is more commonly thought of as "inflammation", which may be caused by viruses, bacteria (e.g., H.pylori), radiation and other factors that may undermine individual immune systems from effectively dealing with it. BTW, id you look at CPTP, it specifically blocks cellular mechanism of inflammation.

Instead of trying to track down the apparently very elusive cause(s), which we have had little success after all these years...

Actually, the study is independent and differs from others in that it is a "macro" study, trying to "classify" common cancer "causes" scientifically based on DNA mutations signatures rather than ad hoc "environment" categories based on often flawed observations or even often fraudulent group biases (political, racial, dietetic, environmental etc.).

It already reduced "common cause" of more than 200 cancers down to 21 signatures, which may lead to better understanding and discovery of commonality and reduction of numbers and higher effectiveness of treatments. It may also happen that only a subset of these 21 signatures is relevant, further reducing the amount of effort needed for advancement of screening.

In addition (rather than "instead of"), this study is complementary to others in that it might significantly reduce the number of false assumptions and allow other scientists to deal with only certain genetically significant signatures.

Far from being [nearly] useless, this study may turn out to become a specific "reference" study, sort of Cancer Genome Project.

Even with our advances in technology and research capabilities, we definitely can use some serendipity to make a breakthrough like in the old days.

Serendipity and Eureka moments happen every day, even within the large "cold" prim scientific studies, only they are now based on [hopefully] better scientific knowledge and understanding. Count on it! :-)

Also take a look at the second article, within my first comment - probably a serendipitous development of someone taking a look at part of "junk DNA" and finding a possible cancer cure.

[sun7]

Can’t disagree with the things you said and, I don’t have any more specifics because everything I know comes from what I read. Thank you very much for taking the time to critique my comment; now no one can come away with any misunderstanding of what’s going on.

I did skim through everything in your post #2 before commenting. It would be a big time-saver if only we knew which 20% of an article to read to get 80% of the information. By the way, I pointed out what I considered irrelevant from another poster after reading enough to know what both articles are about, not as a result of missing something.

And to set the record straight on serendipity, I actually firmly believe almost everything we attribute to luck or accept as random are anything but.

[CutePuppy]

And to set the record straight on serendipity, I actually firmly believe almost everything we attribute to luck or accept as random are anything but.

Definitely. There is a saying I was fortunate to hear early in life:
"It takes a lifetime of effort and determination to become an overnight success."