International study sequences the genomes of pancreatic cancer cases

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International study sequences the genomes of pancreatic cancer cases

A large international collaborative study was published on October 24, 2012 in the highly esteemed journal Nature. The study was primarily conducted by the Australian pancreatic cancer team of the International Cancer Genome Consortium (ICGC). In addition to the researchers in Australia, scientists from various US institutions were also involved, including Johns Hopkins University, University of California San Francisco, and Mayo Clinic. Represented among the US-based ICGC team are several Pancreatic Cancer Action Network research grant recipients, in addition to multiple current and emeritus members of the organization’s Scientific Advisory Board.

The researchers sequenced the entire genome of pancreatic tumor tissue samples from over 100 patients, and the resulting sequence was compared to each individual’s normal DNA, to reveal genetic changes involved in the progression to pancreatic cancer. The samples were obtained from surgical removal of the patients’ tumors, and therefore all the specimens represented small tumors at early stages of the disease.

Reinforcing previous findings, the investigators detected mutations in several genes that are well known to be critical to the growth and progression of pancreatic cancer. For example, consistent with others’ results, over 90 percent of pancreatic cancer specimens evaluated were found to express a mutant version of the gene K-Ras.

By comparing tumor to normal DNA of the same patients, the research team was also able to identify additional genetic changes that were not previously known to be involved in pancreatic cancer progression. Some of these changes occurred quite infrequently, and were only observed in one or a few cases. Other previously undiscovered genetic changes were a bit more prevalent, such as mutations to the axon guidance pathway (controls how brain cells connect to each other), and further studies will be necessary to explain why these genes play a role in pancreatic cancer. The wide genetic variation seen in these samples highlights the complexity of pancreatic cancer, and is among the reasons why this disease is so difficult to study and treat.

Identification and a deeper understanding of novel genetic changes that influence the development and progression of pancreatic cancer will be a huge asset to the field. Knowing the genetic changes responsible for the transformation of normal cells into cancer cells could provide clues to ways to detect the disease earlier, as well as revealing genetic targets that could be manipulated in efforts to treat pancreatic cancer.

Click here for the scientific abstract of the study.