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Study Identifies Genes Associated With Improved Survival for Patients With Pancreatic Cancer

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Key Points

  • Using whole-exome sequencing and targeted genomic analyses of 77 other tumors, the study identified mutations in chromatin-regulating genes MLL, MLL2, MLL3, and ARID1A in 20% of patients with pancreatic cancer associated with improved survival.
  • Using a liquid biopsy analysis, researchers also found that 43% of pancreatic cancer patients had circulating tumor DNA in their bloodstream at the time of diagnosis.
  • Detection of circulating tumor DNA following surgery predicts clinical relapse of the cancer and poor outcomes for patients. In addition, using a liquid biopsy detected the recurrence of cancer 6.5 months earlier than using CT imaging.

A multi-institutional study has found a new set of genes that may indicate improved survival after surgery for patients with pancreatic cancer. The study also showed that detection of circulating tumor DNA in the blood could provide an early indication of tumor recurrence. In conjunction with the Stand Up To Cancer (SU2C) Pancreatic Cancer Dream Team, the study was published by Sausen et al in Nature Communications.

Study Findings

Using whole-exome sequencing and targeted genomic analyses of 77 other tumors, the study identified mutations in chromatin-regulating genes MLL, MLL2, MLL3, and ARID1A in 20% of patients associated with improved survival. Researchers, using a liquid biopsy analysis, also found that 43% of patients with pancreatic cancer had circulating tumor DNA in their bloodstream at the time of diagnosis. The pancreatic cancers analyzed in the study were stage II tumors from patients who underwent potentially curative surgery.

The study also found that detection of circulating tumor DNA following surgery predicted clinical relapse of the cancer and poor outcomes for patients. In addition, using a liquid biopsy detected the recurrence of cancer 6.5 months earlier than using computed tomography imaging.

Implications of Results

“These observations provide predictors of outcomes in patients with pancreatic cancer and have implications for detection of tumor recurrence, and perhaps someday for early detection of the cancer,” said Daniel D. Von Hoff, MD, FACP, Translational Genomics Research Institute (TGen) Distinguished Professor and Physician-In-Chief, Codirector of TGen’s SU2C Pancreatic Cancer Dream Team, and Chief Scientific Officer at the Virginia G. Piper Cancer Center Clinical Trials at HonorHealth.

The study's results found that a significant number of early-stage pancreatic cancers could be diagnosed noninvasively using liquid biopsy blood analysis that focuses on a few specific genetic alterations.

“We have identified MML genes as markers of improved prognosis for patients with pancreatic cancer,” Dr. Von Hoff said. “We have also shown that circulating tumor DNA in the blood of pancreatic cancer patients may provide a marker of earlier detection of recurrence of the disease.”

This analysis suggests that additional studies should “evaluate more intensive therapies” for patients without MLL mutations or with detectable circulating tumor DNA following surgical removal of their tumors, as well as interventional clinical trials.

Participants in this study included the Translational Genomics Research Institute, Johns Hopkins University School of Medicine, Mayo Clinic, and Memorial Sloan Kettering Cancer Center.

Victor E. Velculescu, MD, PhD, of Johns Hopkins Medicine, is the corresponding author of the Nature Communications article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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