Hidden Cancer Risks for Women Found in Genome Analysis
An analysis of the most common uterine cancer suggests the disease should be reclassified into four categories that may help lead to more targeted treatments.
About a quarter of a group of women who would be thought to have a favorable outcome under traditional diagnosis, or 10 percent of all patients, actually have genetic changes suggesting they have a more serious disease and may be in need of more aggressive treatment, according to the research in the journal Nature. A second DNA study of cancer in the New England Journal of Medicine describes almost all the major mutations in acute myeloid leukemia.
The two papers released yesterday are part of the Cancer Genome Atlas project, a U.S. National Institutes of Health effort to discover what changes make a normal cell cancerous and pinpoint more effective treatments. The work may mark the beginning of a shift from organ-based cancer research to gene-based research, said Michael Melner, scientific program director at the American Cancer Society, who wasn’t involved in the research.
“What’s becoming more and more evident is the potential that we can segment patients not based on the organ system where they have cancer, but the genetic defects the cancer has,” he said. “There might be lung cancers that are more genetically similar to brain cancers than to other lung cancers, and so they may be more appropriately treated with brain cancer drugs.”
The Cancer Genome Atlas is looking at 20 types of cancer to understand the key mutations for the disease, said Richard K. Wilson, the director of the Genome Institute at Washington University in St. Louis. Right now, doctors consider the organ system, take a sample of the cancerous cells, and look at them under the microscope to determine the type.
Previous results from sequencing breast cancer, lung cancer and colon cancer were released last year. The approaches may lead to new therapies and help provide better care for current patients with existing treatments, doctors said.
The most common form of uterine cancer is found in the cells lining the womb, called the endometrium. The National Cancer Institute estimates that almost 50,000 new cases of endometrial cancer will be diagnosed this year in the U.S., and about 8,000 women will die of the disease.
In the endometrial cancer study, researchers analyzed tumors from 373 women to look for changes. Two current categories are used for endometrial cancer: endometrioid and serous. The former type is typically associated with obesity and has a favorable prognosis, while serous cancers usually have poorer outcome.
Serous and endometrioid cancers are diagnosed by pathologists looking under a microscope. However, by looking at the genomic level, yesterday’s report found the endometrioid tumors that were most likely to grow and spread shared genetic features with the serous type, including alterations in the number of copies of a gene.
The finding suggests that women whose cancer has abnormal copies of a gene may be better treated by chemotherapy, which is more aggressive, rather than by radiation, after surgery. That hypothesis should be tested in clinical trials before practice is changed, the authors wrote.
“This kind of study can have a direct impact on patients,” said Douglas Levine, a surgeon and the head of the gynecology research laboratory at Memorial Sloan-Kettering Cancer Center in New York. “We want to match the aggressive treatment with aggressive cancers, and spare people with low-risk disease the unnecessary toxic treatments.”
Another subgroup, with an extremely high number of mutations, does better than others, Levine said. It may be worth testing to see if this group needs anything beyond surgery at all, he said.
In the leukemia study, 200 people were analyzed. Acute myeloid leukemia has fewer mutations than other adult cancers, the authors wrote. Although 237 genes were mutated in two or more samples, only 23 were significantly mutated.
“It doesn’t take much to turn a cell into a leukemia cell, but there are a lot of different paths,” said Washington University’s Wilson.
Acute myeloid leukemia, a cancer of the blood and bone marrow, will be diagnosed annually in about 15,000 people, mostly adults, according to the American Cancer Society. About 10,000 patients will die each year of the disease.
About 60 percent of the tumors had changes in signaling genes, which communicate with other cells. That may be part of what prompts the abnormal growths, Wilson said. Another 44 percent of the mutations found affected the way that proteins interact with DNA. That may make it easier to turn on certain genes or to block their function.
“We need to dig a little deeper and get to a point where that’s part of the diagnosis, to tailor treatment to what we find in the genome,” Wilson said.
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