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Bluestar Genomics Scientists Non-Invasively Detect Epigenomic Signatures of Early Pancreatic Cancer

September 24, 2018

SAN FRANCISCO--(BUSINESS WIRE)--Sep 24, 2018--Bluestar Genomics, a company developing innovative, data-driven, epigenomic approaches to comprehensive disease analysis and diagnostics, today reported research identifying specific epigenomic biomarkers of early pancreatic cancer within cell-free DNA, potentially enabling future non-invasive diagnostics using liquid biopsy samples (1).

Despite extensive translational research into the genetic drivers of pancreatic cancer, few molecular advances have been made in the development of new therapeutics or diagnostic biomarkers to improve five-year survival outcomes. Pancreatic cancer is the deadliest of all major cancers, with only an 8% five-year survival rate from diagnosis, as it is often diagnosed only at late stage given there are few early symptoms. It is the third leading cause of cancer death, killing over 44,000 people in the United States in 2018, following only far more prevalent lung and colorectal cancers (2); unlike these more prevalent cancers, pancreatic cancer has no recommended tools for early detection (3). Bluestar Genomics’ research is a significant advancement toward a liquid biopsy tool to help clinicians and biomedical researchers more precisely identify and stratify pancreatic cancer patients earlier.

“We are excited by this data since it moves the needle closer to a future where high-precision, non-invasive disease testing is the norm for patients,” said Dr. Stephen Quake, Professor, Bioengineering and Applied Physics at Stanford University, Co-President, Chan Zuckerberg Biohub, and Bluestar Genomics’ Scientific Advisor. “That is going to require a comprehensive approach to developing diagnostics, using synergistic technologies like precision epigenomics and liquid biopsy samples, and this research is a significant step on that path.”

Encouraged by their previous research defining tissue of tumor origin using epigenomic signatures (4), Bluestar Genomics’ researchers moved beyond the limitations of genomic sequencing alone, using epigenomic analysis to identify potentially actionable biomarkers from 5-hydroxymethylation patterns in the cell-free DNA from pancreatic cancer patients. Developing these biomarkers in a liquid biopsy format provides important new non-invasive tools, free from the current limitations of direct observation of overt symptoms, late in disease, or of earlier incidental radiological findings, not specific to pancreatic cancer.

The cell-free, DNA-based epigenomic study used a retrospective case-control design with plasma samples obtained from non-cancer subjects, as well as archived plasma previously obtained from patients who underwent surgical resection for pancreatic cancer with a confirmed diagnosis of pancreatic ductal adenocarcinoma (PDAC), the predominant form of pancreatic cancer. A total of 92 subjects satisfied the study eligibility criteria, including 41 non-cancer subjects and 51 PDAC subjects. Significantly different epigenomic signatures — including areas of enrichment and absence of 5-hydroxymethylation — were discovered between the two sample groups and used to construct predictive models to distinguish pancreatic cancer and non-cancer patients. “By combining a novel 5-hydroxymethylation enrichment assay with high throughput sequencing, it was possible to generate powerful predictive models to enable the classification of pancreatic cancer patients with high accuracy,” added Samuel Levy, Bluestar Genomics’ Chief Scientific Officer.

“Until recently, liquid biopsy genomics has traditionally focused on detecting mutational sequence differences in cell-free DNA. This has generally limited clinical applications to those conditions where specific diagnostic sequences exist and can be attributed to the disease sources, such as from a tumor or pathogen,” said Bluestar Genomics’ Chief Executive Officer Patrick Arensdorf. “We see much greater potential combining next generation sequencing with the analysis of global patterns of epigenomic characteristics, such as DNA hydroxymethylation, in order to provide novel biological and clinical information. This research takes a significant step towards improved diagnostics for a broader range of health conditions, including the need for earlier diagnosis of pancreatic cancer.”

The research results, authored by Francois Collin et al., are available online at the BioRxiv.org preprint server, where the authors welcome manuscript feedback.

Collin et al. (2018) ‘Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA’. Biorxiv 422675. [ http://doi.org/10.1101/422675 ]. Siegel et al. (2018) ‘Cancer Statistics, 2018’. CA: A Cancer Journal for Clinicians, 68 (1) pp. 7-30. [ http://doi.org/10.3322/caac.21442 ]. Sauer et al. (2017) ‘Updated review of the prevalence of major risk factors and use of screening tests for cancer in the United States’. Cancer Epidemiology, Biomarkers, and Prevention, 26 (8) 1192-1208. [ http://doi.org/10.1158/1055-9965.EPI-17-0219 ]. Song et al. (2017) ‘5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages’. Cell Research, 27, pp. 1231-1242. [ http://doi.org/10.1038/cr.2017.106 ]

About Bluestar Genomics

Bluestar Genomics develops next-generation epigenomic approaches to non-invasive molecular testing to provide novel insight and quantification of human health and disease to improve healthcare outcomes. Founded out of the Stanford laboratory of Dr. Stephen Quake, Bluestar Genomics combines biological ingenuity with AI and big data analysis to tackle the most urgent challenges in oncology, immunology, neurology, cardiovascular disease and beyond. Leveraging the ease of liquid biopsy technologies, the company’s cell-free DNA-based assays are targeting large, unmet clinical needs, using simple and non-invasive samples to improve healthcare outcomes. Led by a team with decades of experience bringing products from concept to market, Bluestar Genomics is continuously seeking better ways to measure disease pathology and bring its technologies to the patients, clinicians and scientists searching for tomorrow’s cures.

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SOURCE: Bluestar Genomics

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PUB: 09/24/2018 09:00 AM/DISC: 09/24/2018 09:01 AM

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