03:36pm Monday 11 December 2017

Brain Tumor Consortium narrows search for familial glioma susceptibility

The report online in the journal Cancer Research involved analysis of the genotype or genetic makeup of 75 families in which there were two or more members who had had glioma – a common form of adult brain cancer and the most deadly.

In total, the researchers led by Professor Melissa Bondy at Baylor College of Medicine and including Dr. Elizabeth B. Claus of the Department of Neurosurgery at Brigham and Women’s Hospital, determined the genotype or genetic makeup of 46 families in the first phase of the study and 29 in the second, confirmatory phase. The researchers are part of the Genetic Epidemiology of Glioma International Consortium, which consists of 15 institutions in the United States, the United Kingdom, Sweden, Denmark and Israel.
Hunting for mutations.

Their analysis of the massive amounts of data pointed to a particular region on chromosome 17 called 17q12-21.3. The next step will be to sequence the region in family members with glioma, and in those without, seeking to find mutations that could cause disease.
“Previous studies have shown that inherited susceptibility plays a role in glioma,” said Bondy, a corresponding author of the study. “First-degree relatives show a two-fold increased risk of the disease.”

“In this study, each of the sites collected families with glioma, a difficult undertaking for such a lethal disease,” said Claus. “The families were then genotyped using an approach similar to the genome-wide association studies.” In addition to the U.S. families in this study, the group has identified as many as 1,000 such families worldwide – the largest collection of families with a least two family members who have had glioma in the world.

The plan to follow the families they have identified to determine how important this region is in the risk of glioma. Already, one person who was believed unaffected by the disease in one family has developed glioma.

Funding for this study came from the National Institutes of Health, the Brain Science Foundation, the American Brain Tumor Association, the National Brain Tumor Society and the Tug McGraw Foundation. For more information on the consortium, please go to Gliogene.

Investigators include Robert K. Yu, Georgina N. Armstrong, Sanjay Shete, and Yanhong Liu of MD Anderson; Melissa Bondy, Eastwood Hon-Chiu Leung, Caleb Davis, Rita Cheng of the Dan L. Duncan Cancer Center at BCM; Richard S. Houlston and Fay J Hosking of the Institute of Cancer Research, Sutton, United Kingdom; Elizabeth B. Claus of the Yale University School of Medicine, New Haven, Conn., and the Brigham and Women’s Hospital, Boston, Mass.; Jill Barnholtz-Sloan of the Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio; Rose Lai of the Neurological Institute of Columbia University, New York; Dora Il’yasova and Joellen Schildkraut of Duke University Medical Center, Durham, N.C.; Siegal Sadetzki of the Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Christoffer Johansen of the Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Jonine L. Bernstein and Sara H of Memorial Sloan-Kettering Cancer Center, New York; Robert B. Jenkins and Ping Yang of Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minn.; Beatrice S. Melin and Roger Henriksson of Umeå University, Umeå ,Sweden; Nicholas A. Vick of Evanston Kellogg Cancer Care Center North Shore University Health System, Evanston, Ill.; Margaret Wrensch of University of California, San Francisco; and Bridget J. McCarthy and Faith G. Davis of University of Illinois at Chicago.


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