Gene Studies Reveal Cancer's Secrets

TUESDAY, April 21 (HealthDay News) -- A close look at a tumor's or patient's genetics can provide important, potentially lifesaving clues to preventing and treating cancer.

So say scientists who outlined their research Tuesday in five presentations at the American Association for Cancer Research's annual meeting, in Denver.

"This is an interesting set of presentations," John S. Witte, a professor in the Institute for Human Genetics at the University of California, San Francisco, said during a midday press conference. "All the studies have an impact on the potential to predict risk or recurrence or response to treatment," he said.

In the first study, researchers led by Dr. Charles Mullighan, an assistant member at St. Jude Children's Research Hospital, Memphis, found that children with acute lymphoblastic leukemia (ALL) who have mutations in the JAK tyrosine kinase gene generally have poor outcomes, including a higher risk of recurrence of their cancer. The finding suggests the gene could be a potential diagnostic tool and a new therapeutic target.

Despite improvements in treatment, some children with ALL will relapse, Mullighan told reporters.

For the study, the Memphis team analyzed the genes of 221 children with the disease.

Although JAK mutations were not previously known to occur in children with ALL, they were discovered in 10 percent of these patients. The mutations were associated with a deletion of the genes IKZF1 and CDKN2A/B and poor outcome. And, over four years, 71 percent of the children with JAK and IKZF1 alterations had a relapse of their disease, compared with only 23 percent for patients without these genetic alterations, the researchers found.

But there was good news, too. "When we treated the cancer cells with a JAK inhibitor, the cells died," Mullighan said. "This suggests that these JAC mutations are a new therapeutic target in this subtype of leukemia."

Another study on leukemia found that a set of genetic variants increases the risk for chronic lymphocytic leukemia (CLL). The findings of this study add more pieces to the puzzle and could lead to better prevention and prognosis of the disease, according to lead researcher Susan Slager, associate professor of biostatistics at the Mayo Clinic in Rochester, Minn.

About 15,000 Americans will develop CLL each year, and 4,000 will die, so it is one of the rarer cancers, Slager said during the teleconference. However, "if you have a family member with chronic lymphocytic leukemia, your chances of getting the disease are eight times higher than that of the general population," she noted.

An earlier analysis identified seven DNA sequencing aberrations called "single nucleotide polymorphisms" (SNPs) that might lead to chronic lymphocytic leukemia. In the current study, researchers confirmed these findings in a separate sample of patients. They found the strongest genetic association for the disease was for a SNP on the 11q24 gene, where the risk was 50 percent higher. This was followed by a 39 percent increased risk with a separate SNP on the 6p25 gene.

"Our findings will hopefully understand the biology of the disease, which may help us predict the disease, and it may help us develop better treatments and prognostic markers," Slager said.

Results of another study presented at the meeting showed that genetic variants in what's known as the microRNA processing pathway may predict a woman's risk for ovarian cancer.

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