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Showing How Genetic Changes Affect Lymphoma Survival

Joseph Hacia, an assistant professor of biochemistry and molecular biology

A multicenter, multinational team of researchers, led by Joseph G. Hacia, assistant professor of biochemistry and molecular biology at the Institute for Genetic Medicine of the Keck School of Medicine of USC, has made unprecedented progress toward identifying molecular and genetic changes that have an impact on survival time in patients with mantle cell lymphoma.

The study recently was published in the Proceedings of the National Academy of Sciences.

Mantle cell lymphomas are aggressive tumors that account for about six percent of all non-Hodgkin lymphoma cases in the United States.

“In our paper, we took genomic approaches to characterize molecular changes frequently found in mantle cell lymphomas,” Hacia said.

“We recognize that mantle cell lymphoma is a blanket term for a number of highly related cancers that nonetheless have different clinical outcomes, such as time of survival after diagnosis,” he added.

For example, while the median survival for a patient with mantle cell lymphoma is three years, some individuals live for more than 10 years after being diagnosed.

It makes great sense, then, that scientists and physicians would like to be able to determine which mantle cell lymphoma patients have a better prognosis than the others � and why.

Most studies trying to connect these clinical outcomes with molecular or genetic alterations that might allow for such pinpointed prognoses are only able to look for a single broad alteration in a given cancer. But this study, Hacia said, is different.

“We were able to correlate multiple classes of molecular alterations �namely ATM [ataxia telangiectasia mutated] and p53 mutation status �gene expression profiles and some chromosomal abnormalities within themselves and with overall survival,” he said. “One exciting part of the project is that we could find links among these molecular changes that made perfect sense � for example, large deletions of chromosomal segments lead to decreased expression levels of genes within these segments.”

Ultimately, Hacia’s study found that patients in whom the p53 tumor suppressor gene had been inactivated had a slightly reduced overall survival time. “In addition,” he added, “we were able to elucidate gene expression changes occurring in p53 mutant mantle cell lymphoma cases that may be relevant to their poor prognosis.”

On the other hand, those in whom the ATM gene was either mutated or deleted did not have a significant disadvantage in survival time.

In addition to the participation of several Keck School scientists, Hacia was part of a team consisting of researchers from the University of Nebraska Medical Center in Omaha; the University of Oregon in Portland; the University of Barcelona in Spain; the Norwegian Radium Hospital in Oslo; the British Columbia Cancer Agency in Vancouver; the National Cancer Institute in Bethesda, Md., and the University of Wurzburg in Germany.

The work was supported by grants from the Margaret E. Early and L.K. Whittier Foundations, the V Foundation for Cancer Research, the National Cancer Institute, the Lymphoma Research Foundation Mantle Cell Grant program and the Intramural Research Program of the National Institutes of Health.

Showing How Genetic Changes Affect Lymphoma Survival

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