Researchers at MD Anderson have found that pancreatic cancer tumors essentially spill their molecular secrets when they shed their complete DNA and RNA — wrapped inside protective lipid particles — into the bloodstream. This makes the tumors ripe for analysis with a liquid biopsy, according to a recent online report in the Annals of Oncology.
The scientists conducted whole genome, whole exome and gene expression analysis of tumors in three patients using DNA and RNA found inside exosomes circulating in their blood or other liquid biospecimens.
“Analysis of exosomal DNA and RNA allows us to do everything you can do off a direct biopsy of tumor tissue,” said senior author Anirban Maitra, M.B.B.S., professor of Pathology and director of MD Anderson’s Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research.
The research was conducted as part of MD Anderson’s Moon Shots Program, which seeks to accelerate development of clinical and prevention advances from scientific knowledge. Maitra is co-leader of the Pancreatic Cancer Moon Shot, one of 12 in the program.
The proof of principle study opens the door to validation studies in multiple tumor types of a liquid biopsy that could be used to determine prognosis, guide targeted therapy and monitor treatment.
Meeting pancreatic biopsy challenge
Maitra and colleagues detected a variety of cancer-derived biomarkers, including genetic mutations, insertions, deletions, copy number profiles and gene fusions that can act as neoantigens — new targets for the immune system. Potentially treatable mutations, including BRCA2 and NOTCH1, were identified.
Analyzing gene expression
“Full RNA sequencing is important because genome sequencing tells you what genes are altered, while analysis of RNA tells you what abnormal genes are actually being expressed,” he said. “Shed exosomes allow us to do matched DNA and RNA simultaneously in liquid biopsies at a resolution that is not amenable with cell-free approaches.”
Common clinical practice now calls for only a pretreatment biopsy in deeply located tumors at presentation. Conducting biopsies during treatment would more closely monitor therapy success or failure and help researchers better understand how the cancer genome evolves in response to treatment.
Exosomes may actually paint a more complete picture of a tumor's genomic diversity because all genetic mutations present in primary and metastatic tumors would flow into a liquid biopsy via the exosomes, the researchers noted. Sampling part of a tumor might only capture mutations in that area and not reflect its overall genomic diversity.
Exosomes were isolated from blood samples in two patients and also from pleural fluid in a patient who had lung metastases. Whole genome sequencing covered up to 91% of the human genome while exome sequencing of only the protein-coding genes covered 95 to 99%.
Learn more about the search for a pancreatic cancer biopsy on MD Anderson’s website.