Cigarettes and sunlight leave their mark on cancer genomes

Date 2009 12 17

Details of the first ever cancer genome sequences are released in two papers published online by the journal Nature. The studies reveal that the genetic sequence of the lung cancer cell line bears all the hallmarks of DNA damage caused by tobacco smoke, while many of the mutations in the melanoma tumour are characteristic of the kind of damage inflicted on DNA by exposure to ultraviolet (UV) light. The sequences also contain traces of the cells’ efforts to repair the damaged DNA.

The researchers behind the papers, from the Netherlands, the UK and the US, hope that their work will eventually lead to tailored treatments for cancer in which drugs are chosen on the basis of the mutations identified in their cancer.

‘This is the first glimpse of the future of cancer medicine, not only in the laboratory, but eventually in the clinic,’ commented Sir Mark Walport, Director of the Wellcome Trust Sanger Institute in the UK. ‘The findings from today will feed into knowledge, methods and practice in patient care.’

Cancer cells contain genetic mutations that have built up over a person’s lifetime. In these studies, the scientists used the latest DNA sequencing technology to map the genomes of a malignant melanoma and a small cell lung cancer (SCLC). The team also decoded the genome of healthy cells taken from two patients. By comparing the two, the team could pick out the genetic mutations specific to the cancer.

‘Mutations in DNA caused by, for example, cigarette smoke, are passed on to every subsequent generation of daughter cells, a permanent record of the damage done’ explained Dr Andy Futreal of the Wellcome Trust Sanger Institute. ‘Like an archaeologist, we can begin to reconstruct the history of the cancer clone revealing a record of past exposure and accumulated damage in the genome.’

Lung cancer causes around 1 million deaths worldwide every year, making it the leading cause of cancer related deaths. SCLC in particular accounts for around 15% of lung cancer cases. It is notoriously hard to treat, and most patients die within two years of diagnosis.

The majority of lung cancer cases are caused by smoking. Tobacco smoke contains over 60 chemicals that attack DNA, causing mutations. The team recorded over 20,000 mutations in the lung cancer cells. While most of these mutations are harmless, some cause the cell to become cancerous.

‘For the first time, we have a comprehensive map of all mutations in a cancer cell,’ commented Dr Peter Campbell of the Wellcome Trust Sanger Institute. ‘The profile of mutations we observed is exactly that expected from tobacco, suggesting that the majority of the 23,000 we found are caused by the cocktail of chemicals found in cigarettes. On the basis of average estimates, we can say that 1 mutation is fixed in the genome for every 15 cigarettes smoked.’

The analysis also revealed the efforts the cells’ repair systems had made to fix the damaged DNA, and even uncovered evidence of an undiscovered system of DNA repair that tackled mutations in highly active genes. This implies that the cell seeks to protect these parts of the genome above many others.

The second study focused its efforts on a sample taken from a patient with malignant melanoma. Although it only accounts for 3% of skin cancer cases, malignant melanoma is responsible for three quarters of skin cancer deaths.

The melanoma genome turned out to harbour over 33,000 mutations, many of which are precisely the kinds of mutations associated with exposure to UV light. ‘It is amazing what you can see in these genomes. UV light induced mutations leave a typical signature, forming the vast majority of the mutations,’ said Dr Campbell. ‘Indeed, because of the clarity of the genome data, we can distinguish some of the early, UV induced mutations from the later mutations that do not have this signature.’ The researchers suspect that these later mutations arose after the cancer cells had spread from the skin to tissues deeper inside the body.

The next step for the researchers is to study the new sequences in greater detail to determine which mutations caused the cells to become cancerous.

‘Cancer is driven by acquired mutations in genes, and we are at a point where it soon will be possible to actually know every mutation in the tumours of each of our patients,’ commented Dr John Minna of the University of Texas (UT) Southwestern Medical Center in the US. ‘The key will be to use this information to find new ways to help prevent cancers, diagnose them earlier and to select treatments that might be specific for each patient’s tumour. While these findings are the first step, they have lighted our path to clearly point us in the right direction.’

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Wellcome Trust Sanger Institute

University of Texas Southwestern Medical Center

Related stories 30632, 30969, 31237

Category Miscellaneous
Data Source Provider Nature Wellcome Trust UT Southwestern Medical Center
Document Reference Pleasance, E.D. et al, DOI 10.1038/nature08629
Pleasance, E.D. et al, DOI 10.1038/nature08658
Both published online by Nature on 16 December 2009.
Subject Index Coordination, Cooperation Life Sciences Medicine, Health Scientific Research

RCN 31597

Changing lifestyle / new york skinny vs paris skinny – garance dore

Marlboro red cigarettes

Moving abroad is much more than a new apartment and a new subway card. It’s a total change, a shift of what seems important, a questioning of priorities and this series of small shocks that you can’t really talk about when they come because there’s no perspective. You don’t yet understand them.

The first thing that struck me was the relationship New Yorkers have with their bodies. A few months back, I was laughingly observing it all, and now I’ve almost completely changed my style of life. Here’s why&#8230

Have you ever had lunch with a New Yorker?

Really, it’s not far from an episode of Sex and the City.

Up close too, the girls are perfect head to toe, and all the way to their nails. They’re rosy cheeked, perfect hair, and their outfits, even if they’re vintage, all seem brand new. And they are really, and I mean really, skinny.

Okay, so I gotta say that when I first arrived in New York, the first people I met all worked in fashion. Then I met lots of other girls and I can say that not ALL New Yorkers are like that. Not all of them.

But the women in fashion in New York, they’re not just skinny. They’re New York skinny. New York skinny means thin to the brink, yet muscly from Pilates because it gives you those super long lean muscles. Anna Wintour style&#8230 Muffin top? What’s that mean?

It was cute, at first, to be the only Parisian at a New Yorker lunch.

But now, have you ever had lunch with Parisians? Well all right Have you ever had lunch with me?

Lunch usually involves a glass a wine, one or two desserts that everyone shares, no need for an appetizer but stuffing your face full of half the bread on the table is kind of totally ok. Finish with a coffee and twelve cigarettes, saying that no, it’s no good, but so much fun.

So it was cute to be the only Parisian at a table of New Yorkers. They would watch me rip another piece of bread off, order a glass of wine and a dessert and ask me what was the secret of those Parisians who stay thin despite such a devastating diet.

And I’d just laugh saying that everyone in NY is just too skinny, that they have to live a little and no, I don’t work out at all cause I have so many other fascinating things to do in my life. Like smoking a few cigarettes, just to name one. And I’m perfectly fine with my little muffin top, thank you. I was perfectly happy that way.

This whole little game went on for a while just like that.

Until, actually, my muffin top took on a mind all its own. I swear, I couldn’t get my skinny jeans to button. There, all of a sudden, I started to shut up. I stopped being smug at lunch. I saw it right there. I gained weight. I gained weight like I’d never gained weight before.

That’s when I first started to understand some of the many differences between the Parisian and New York diet.

1 / The restaurants Yes, Parisians will just let it all go ten times more when they go out. But they’re 10 times less likely to go out as well. And in Paris, no take out&#8230 You cook. In New York, your social life happens outside the house. You have meals out. The only time I “cooked” since I got to New York, it was to make crepes to show just how French I was.

2 / The portions Have you ever seen the size of plates in New York? BIG. You understand right away the doggy bag concept that makes everyone laugh in France. Really though, with one plate, you could easily make two real meals out of it. But unfortunately your eyes and body get accustomed so fast to the giant mounds and you find yourself finishing your entire plate without even realizing it.

3 / The dietary norms So maybe this isn’t something I can speak abut as I don’t know anything about that, but one thing’s for sure, the laws are totally different about things like what growth hormones you can feed beef and chicken to make them grow faster. I don’t know how all this affects our weight, but I don’t see how it could help but get into the milk, eggs and meat. It’s crazy. I was talking with Emily, my Australian friend who just got here to NYC and she also gained 10 pounds just like that (It’s known as the little house warming gift in NYC Hello! Welcome! Here’s 10 pounds!). Plus here, not only did were we getting fatter the fat seemed softer. Yeurk.

Here are just a few things that would end up making anybody a little paranoid of food&#8230 And end up with extremes&#8230 Work out to lose weight and here, working out is an every day activity, eat less, worry about where your food is coming from, decide to stop eating meat, or gluten, milk, or just all that stuff all together&#8230 And become New York skinny.

And then after that, there’s another thing that pushes this weight loss obsession and that’s social status. “My mom always says, ‘the smaller the dress size, the larger the apartment.” I once read that in the New York Times. It’s funny, but totally baffling, right? Oh New York social status&#8230 Just let me digest for a second (ahah) and we’ll get back to it later.

I feel like there wasn’t that same pressure in Paris.

That isn’t to say that Paris is a paradise of health and self acceptance, but just that it’s less about extremes.

But with me, stuck between the obsession of skinny in New York, my overly relaxed Parisian attitude, and the pounds that keep adding up behind my boastful smile, it was maybe time for me to ask myself questions about my lifestyle&#8230 And look at myself in a mirror.

Oh my gaaaaaad. Life’s tough.

To be continued!!! Big hugs!