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Scientists unearth genetic keys to 2 cancers

Dr. Douglas A. Levine, a surgeon/scientist at Memorial

Dr. Douglas A. Levine, a surgeon/scientist at Memorial Sloan-Kettering Cancer Center in Manhattan, heads the gynecologic cancer research laboratory. He is also a co-leader of endometrial cancer's genomic study. Photo Credit: Robert Lisak

Within days last week, scientists announced discovering the genetic underpinnings of two worrisome malignancies: endometrial cancer, the fourth-leading cause of cancer in women and acute myeloid leukemia, a disease that is often difficult to fight.

The findings were not accidental.

Both were targets of genetic discovery in a vast government-funded project known as the The Genome Atlas of Cancer, first launched as a pilot project in 2005. It has been backed since 2009 with almost $300 million. The plan is to fully identify the genes of 20 forms of cancer.

Scientists who are on the hunt for the molecules of malignancy say their search is turning up some suspected genetic culprits, but is also revealing a few surprises.

"With this latest study in a series of 20," said Dr. Francis S. Collins, director of the National Institutes, "more genomic similarities are emerging between disparate tumor types."

In the search for endometrial cancer's genes, nearly 400 human tumors were studied, experts said.

With that form of cancer, scientists now know as a direct result of atlas project, that a significant proportion of tumors categorized in a milder variant of the disease actually share genetic characteristics with a more virulent form.

"This is really important because it will have a high impact on treatment," said Dr. Douglas A. Levine, a surgeon/scientist at Memorial Sloan-Kettering Cancer Center in Manhattan, who heads the gynecologic cancer research laboratory. He is also a co-leader of endometrial cancer's genomic study.

Before the project doctors knew that endometrial cancers (malignancies of the uterine lining) fell into one of two broad categories: type 1, so-called endometrioid cancers and type 2 tumors, known as serous cancers. Distinguishing one type from the other involved studying thin slices of tumor tissue under a microscope, Levine said, noting there are often disagreements among pathologists about results

Type 1, he explained, correlates with excess estrogen, obesity, and a favorable prognosis. But type 2 more frequently occurs in older women and generally has a less favorable outcome.

In the atlas search, he and his collaborators discovered that an estimated 25 percent of tumors pathologists would have classified as high-grade endometrioid cancer showed a frequent pattern of mutations associated with serous tumors.

Women diagnosed with the endometrioid variant usually undergo radiation treatment while those diagnosed as having the serous form are treated with chemotherapy. It now appears that chemo may be in order for those with the more aggressive endometrioid tumor, Levine said.

"All treatments and drug development stems from understanding the biology of the disease," he added. "These types of studies allow us to take a more comprehensive view.

"We now know where to look and have a road map," he said of the genetic findings. Details of Levine's research were reported last week in the journal Nature.

At Long Island's Cold Spring Harbor Laboratory, Alexander Krasnitz, an expert in cancer genetics, said the atlas project is valuable to any scientist conducting cancer research.

"Suppose we have a lab here doing research on this kind of cancer and the researchers want to find the genes that drive that cancer, transform it from normal tissue to cancerous tissue. They might typically look at a cell line or animal models.

"But they cannot do that search blindly, and if they want to concentrate on a feasible number of targets that's where a database like this can be used.

"This is a very good resource," said Krasnitz, who is not involved in the atlas project.

Acute amyloid leukemia, an illness that is frequently a reason for bone marrow drives on Long Island and beyond, was found to have only 13 mutations, according to gene-atlas researchers.

With about 200 patients contributing blood samples to the project, atlas researchers believe they have mapped the entire set of genes that cause the disease. Complete atlas-research findings were reported in the New England Journal of Medicine on Thursday.

"We now have a genetic playbook for this type of leukemia," Dr. Timothy Ley, associate director of the Genome Institute at Washington University in St. Louis, said in a statement last week. He was colead investigator of the leukemia gene search.

"We don't know all the rules yet, but we know all the major players. This information can help us begin to understand which patients need more aggressive treatment right up front."

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