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Genomic Study Spots Which Tumors Are Deadliest

Genomics signatures in uterine cancers could offer clues to prognosis.

The first comprehensive genomic analysis of endometrial tumors divides the cancer into four subtypes and suggests potential changes to current treatment paradigms. The study, published on Wednesday in the scientific journal Nature, is the latest result of the Cancer Genome Atlas, a U.S.-funded effort to improve cancer treatment with better diagnoses and targeted drug treatments.

The finding “could lead to improved diagnostic approaches and, we hope, to improved therapies,” says Douglas Levine, a surgeon-scientist at Memorial Sloan-Kettering Cancer Center in New York and a leader of the study. The Cancer Genome Atlas studies could one day change oncology so that tumors are not treated based on where they reside in the body, but rather on genomic and other cellular features, says Levine.

Each year, some 49,000 women in the U.S. are diagnosed with endometrial cancer, also known as uterine cancer. Typically, the cancer is classified into one of two groups which correspond to different treatment regimens. But even expert pathologists don’t always agree on how to classify some endometrial tumors, says Levine.

The four subtypes identified in the study are also associated with variable outcomes from one type associated with good prognosis to another that can kill within five years. The researchers identified mutations that are common to each subtype, which could be good targets against which drug companies could develop new, more precise therapeutics (see “Cancer Genomes Let Drugmakers Get Personal”).

“This study fundamentally broadens the molecular understanding of endometrial cancer, and lays the foundation for a new classification of the disease based primarily on cancer genomics,” says Maria Raeder, a gynecologist and scientist at the University of Bergen in Norway. “This will clearly influence the development of new therapeutic opportunities for patients suffering from endometrial cancer,” she says.

But these results are not going to change medical practice immediately. “This would have to be verified on a large scale to show that you can base treatment differences on these characterizations,” says Sarah Temkin, a gynecological oncologist and surgeon at the University of Maryland Greenebaum Cancer Center. “It’s great to be able to identify which patients will have a poor prognosis, but what to do then is not clear.”

The researchers also found some molecular similarities between the most dangerous subtype of endometrial tumors and types of ovarian cancers and breast cancers that are also associated with poor prognosis. This kind of molecular overlap between seemingly distinct tumor types has been uncovered by other Cancer Genome Atlas projects (“see “Similar Molecular Origins for Certain Breast and Ovarian Cancers”). “It broadens our understanding of cancer diseases in general, and suggests that some treatment paradigms may be shared across different cancers,” says Raeder.

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