BY Dan Ferber ? POSTED September 9 2011 AT 11:54 am
Cancer has shown itself to be a wily, relentless foe for labs worldwide, but not an invincible one.? Now a new genomics study, The Cancer Genome Atlas (or TCGA), could help researchers gain the upper hand against ovarian cancer. The study is the most comprehensive analysis of tumor genes yet for any type of cancer, and it opens the door for specific diagnoses and targeted treatments that could save women?s lives.
For decades, researchers searched for mutated genes in cancer cells which could show what went wrong in the cell and offer clues on how to find a drug to make it right. For example, a drug that blocked the activity of the mutated gene?but not its normal cousin?might help stop cancer cells. Such an approach has led to targeted treatments for a handful of cancers such as chronic myeloid leukemia. But for most cancers, the molecular culprits remain unknown, and that?s why ?there?s an overwhelming desire in the [cancer research] community to identify mutations that give rise to cancer,? says Paul T. Spellman, Ph.D., a molecular biologist at Lawrence Berkeley National Laboratory in Berkeley, California.
For years the pursuit moved slowly because it was just too expensive and time-consuming to sequence the entire genomes from hundreds of individual patients. Then, about five years ago, revolutionary genomics technologies arrived and changed that. Next-generation sequencing, for example, allows biologists to determine the DNA sequence of an entire human genome in days, and for just a few thousand dollars! That?s about one ten-thousandth of the $100 million spent to sequence the human genome in the 1990s.
The National Cancer Institute launched TCGA to exploit this new technological prowess in 2008. Their goal: to look across hundreds of tumor genomes to know the spectrum of mutations and other genetic changes that can lead to a particular type of cancer. In other words, they wanted to see the forest to understand its individual trees.
In this study, Spellman and a group of more than 300 TCGA researchers focused on serous adenocarcinoma, which makes up 85 percent of all ovarian cancers and causes 70 percent of the 14,000 ovarian cancer deaths each year in the United States. They determined the entire DNA sequence in the genome of tumors from 489 patients, and tested whether tumors had more or less than the two copies of each gene (one from each parent) that are present in normal cells. Both changes can affect the activity of individual genes, which could take a cell one step closer to becoming cancerous.
Together, the work showed that almost all of the tumors had a mutation in a gene (TP53) that researchers knew protects cells from becoming cancerous. They found that 21 percent of ovarian tumors similarly had mutations in genes called BRCA1 and BRCA2, which are also mutated in many breast tumors. This meant that these two genes helped drive normal cells to become cancerous.
But by examining the entire genome of hundreds of tumors, they came to an additional finding. ?We pretty conclusively showed that genes other than p53 and BRCA1 and BRCA2 did not cause cancer,? Spellman said. ?It?s not what we were hoping to find, but it?s important to know.?
So what had caused cancer in those other cases?
In the June 29 issue of Nature, TCGA researchers reported their finding that tumor cells had too many or too few copies of many genes. In those cases, ?the genome basically gets shuffled,? Spellman says. ?Parts get extra copies, parts lose copies, and parts move around.?
The results differed from what another Genome Atlas team found a few years ago in a brain cancer called glioblastoma, where mutations led most to get the disease. If ovarian cancer was often caused by genome shuffling then other cancers could be, too, Spellman says.
If so, molecular tests that detect abnormal levels of a gene could serve to diagnose a particular subtype of ovarian cancer, and help doctors choose targeted drugs that adjust the activity of that gene. That?s what Herceptin does in patients whose breast tumors have an overactive HER2 gene.
A similar genome mapping effort is in the works for a type of lung cancer called squamous cell adenocarcinoma, and genome maps of 20 other tumor types are planned with money from President Obama?s 2009 economic stimulus. The effort by itself will not overcome cancer, but it will provide a foundation that may lead to targeted treatments for thousands, if not millions, of patients in the future.
CONNECT THE DOTS
Here?s some background on cancer genomics from The Cancer Genome Atlas, and here?s an overview of their efforts. To find out more about Paul T. Spellman?s work, click here.
Source: http://www.healthymagination.com/blog/scientists-make-progress-on-ovarian-cancer-treatment/
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