Spot the Fusion

Pancreatic cancer is one of the deadliest diagnoses a patient can receive. In large part, that’s because of the nature of the disease; most cases of pancreatic cancer aren’t diagnosed until late in their course, meaning that the cancer may be widespread or difficult to treat. Things are looking up in one respect: advances in pancreatic imaging allow doctors to spot lesions earlier than ever and begin tackling disease before symptoms emerge. But surgically resecting lesions can be difficult for both patient and physician, and many such “spots” are harmless cysts or benign tumors that don’t require treatment. How can we tell which lesions are benign and which may lead to cancer?

The answer lies in telomere fusions, genomic alterations that arise when shortened telomeres allow chromosomes to fuse abnormally. Pancreatic lesions that exhibit such alterations have an increased likelihood of progression to cancer, which is why a research group from the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins University School of Medicine has developed a new, PCR-based assay (1). Tissue samples can be obtained through ultrasound-guided fine needle aspiration biopsy, rather than requiring an invasive surgical procedure, and the relatively simple assay involves two rounds of PCR; the first to amplify subtelomeric regions of interest and the second to quantitatively probe the telomere repeat sequence. A positive result indicates a telomere fusion, whereas a negative result can be further checked via gel electrophoresis and additional PCR to avoid false negatives.

In the study, the researchers analyzed normal pancreatic tissue, pancreatic cyst fluid samples, and cancerous precursor (IPMN) tissue, and pancreatic cancer. The assay identified telomere fusions in over half of pancreatic cancers and almost half of IPMN samples with high-grade dysplasia, but spotted none in normal or low-grade dysplastic tissue. Because the fusions are increasingly detected as precancerous tissue progresses toward malignancy, they can serve as a marker for disease and alert doctors to the need to undertake more involved treatment. What’s more, according to study senior author Michael Goggins, there is a further benefit (2): “This telomere fusion detection assay is a cheaper method for evaluating pancreatic cyst fluid than many next generation sequencing approaches that are being evaluated for this purpose.”