Genome analysis of pancreas tumors reveals new pathway
The latest genomic analysis of pancreatic tumors identified two new pathways involved in the disease, information that could be capitalized on to develop new and earlier diagnostic tests for the disease, said a Baylor College of Medicine physician-scientist who was part of the local team that took part in the international effort. A report appears online in the journal Nature.
"We have enormously expanded our knowledge of the genes involved in pancreatic cancer," said Dr. William Fisher, professor of surgery and director of the Elkins Pancreas Center at BCM. "This study ushers in a whole new era of taking care of patients with pancreatic cancer. We will look back on this as a turning point in understanding and treating this disease."
The study follows a five-year collaboration between the Michael E.DeBakey Department of Surgeryand the Baylor College of Medicine Human Genome Sequencing Center, said Fisher. That collaboration began with Dr. Charles Brunicardi, former chair of the department.
New information is much welcome in the field of pancreatic cancer, which is the fourth leading cause of cancer death with an overall five-year survival rate of less than 6 percent. The figures have not changed substantially in the past 50 years.
The study is the first to report findings from primary tumors in the disease. Previously only cell lines or tumors transplanted into mice had been used because the tumors are so small.
"Therefore it required new techniques to sensitively identify mutations that were important to the development of cancer," said Dr. David Wheeler, associate professor in the BCM Human Genome Sequencing Center who oversees the center’s cancer projects.Wheeler and Fisher are also members of the NCI-designated Dan L. Duncan Cancer Center at BCM.
The Baylor College of Medicine Human Genome Sequencing Center was one of three sequencing centers worldwide that analyzed the genomes of pancreatic tumors and normal tissues taken from 142 patients with the disease. The BCM center along with the Australian Pancreatic Center Genome Initiative and the Ontario Institute for Cancer Research Pancreatic Cancer Genome Study carried out detailed studies on 99 of the tumors, identifying 1982 mutations that resulted in a change to a protein and 1,628 significant copy number variations events in which the structure of the chromosomes themselves are changed, either deleting or duplicating genetic information.
The multi-institution, international consortium of researchers discovered mutations in genes involved in chromatin modification (changes that affect the way DNA is packaged inside the cell) and axon guidance (the process by which the axon--a long threadlike project that carries impulses away from the neuron--is guided to grow to its proper target).
"This is a category of genes not previously linked to pancreatic cancer," said Fisher. "We are poised to jump on this gene list and do some exciting things."
Wheeler pointed out that large multi-centered studies using well-annotated groups of patients with cancer are pivotal to studies such as this, which promise to guide the way toward developing new treatment strategies.
Developing such banks of data is part of the goal of the Texas Cancer Research Biobank, said Dr. Richard Gibbs, director of the BCM Human Genome Sequencing Center and a co-author of the report. BCM serves as the coordinating center for the Texas Cancer Research Biobank, which bridges the gap between physicians and researchers. The Biobank is funded in part through the Cancer Research and Prevention Institute of Texas.
Other BCM people who took part include Marie-Claude Gingras, Nipun Kakkar, Fengmei Zhao, Yuan Qing Wu, Min Wang, Donna M. Muzny, Sally E. Hodges, Jennifer Drummond, Kyle Chang, Yi Han, Lora Lewis, Huyen Dinh and Christian Buhay.
Funding for this work came from; the National Health and Medical Research Council of Australia; the Department of Innovation, Industry, Science and Research of Australia; the Australian Cancer Research Foundation; the Queensland Government, the Cancer Council New South Wales; the Avner Nahmi Pancreatic Cancer Research Foundation; the R.T. Hall Trust; the American Association of Cancer Research Landon Foundation; the RACS; the BCM Human Genome Sequencing Center; National Human Genome Research Institute grant; the Cancer Prevention and Research Institute of Texas; The Ontario Institute for Cancer Research; The Ontario Ministry of Economic Development and Innovation and the Canada Foundation for Innovation.