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Focused on Cancer - Follicular lymphoma


TGen and UC Berkeley scientists use ‘pooled’ method to discover gene associated with non-Hodgkin lymphoma

Follicular lymphoma accounts for as much as 30 percent of all non-Hodgkin lymphoma (NHL), a cancer of the lymphatic system involving the blood, bone marrow and lymph nodes.

It was a little outside of his scientific comfort zone, but TGen’s Dr. Kevin Brown jumped at the chance to help researchers at the University of California Berkeley conduct the first genome-wide association study of non-Hodgkin lymphoma.

After all, Dr. Brown once studied the behavior of salamanders during his undergraduate studies, so he’s used to taking on new and unusual tasks.

Dr. Brown, one of the first scientists to join TGen after the biomedical research institute was formed in 2002, has studied skin cancer for most of the past seven years.

But recently, Dr. Brown, an Associate Investigator in TGen’s Integrated Cancer Genomics Division, was asked to work with Dr. Christine Skibola, an Associate Adjunct Professor of Environmental Health Sciences at UC Berkeley’s School of Public Health.

What resulted July 20 was the publication of a scientific paper in the journal Nature Genetics, which identified a gene that carries nearly twice the risk of developing an increasingly common type of follicular lymphoma.

“One of the primary goals of doing a study like this is to be able to look at prevention and early detection strategies. There’s clearly a genetic component to the disease,’’ said Dr. Brown, the study’s co-lead author. “This is a starting point. This gives us new insight into how the disease works. It gives us some potential to target the gene.’’

The investigative team led by Drs. Brown and Skibola identified a single nucleotide polymorphism, or SNP, strongly associated with the risk of developing follicular lymphoma, a cancer whose rates have nearly doubled in the past 30 years.

TGen and UC Berkeley scientists identified the SNP – a particular DNA variant within the more than 3-billion base human genome – as rs6457327.

One of the keys to the study’s success was the use of a “pooled” genome-wide association study, a method of identifying genes championed by Dr. David Craig, Associate Director of TGen’s Neurogenomics Division, and contributor to the Nature Genetics study.

The method has been successfully used at TGen to discover genes associated with other diseases, including Alzheimer’s and metabolic diseases.

This technique allowed the TGen-UC Berkeley team to screen more than 500,000 SNPs. The nearly 90 most significant SNPs were then genotyped to more closely examine their association with lymphoma.

Researchers found that for SNP rs6457327, the presence of the G allele – a DNA letter that varies within the genome – was protective against follicular lymphoma, while the presence of the A allele was predictive of an increased risk of developing follicular lymphoma. Dr. Brown said individuals who had the A variant were nearly twice as likely to develop follicular lymphoma.

Follicular lymphoma accounts for as much as 30 percent of all non-Hodgkin lymphoma (NHL), a cancer of the lymphatic system involving the blood, bone marrow and lymph nodes. In NHL, tumors develop in lymphocytes, a type of white blood cell. Follicular lymphoma arises from B-cells, a specific type of white blood cell. NHL is the fifth most common type of cancer in the U.S., and is newly diagnosed in about 66,000 Americans each year, and annually kills nearly 20,000, according to the National Cancer Institute.

Dr. Skibola said more studies would be needed to determine the biological importance of other SNPs linked to rs6457327 that might change the function of the gene. This could help determine how they might influence risk of the disease.

The scientists also want to know if genetic susceptibility to follicular lymphoma is associated with:

  • Environmental factors, such as exposure to the sun.
  • Conditions such as psoriasis – a chronic, autoimmune skin disease closely associated with a similar region of the genome.
  • Exposure to viruses. Follicular lymphoma is associated with HIV infection, occurring in as many as 10 percent of all HIV-positive patients, according to the Lymphoma Research Foundation.



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