Breaking News
March 24, 2018 - Pubertal hormones not responsible for changes in social behavior during adolescence
March 24, 2018 - Waning Vaccine Protection May Be Driving Rise in U.S. Mumps Cases
March 24, 2018 - Folic Acid in Utero Tied to Food Allergy Risk
March 24, 2018 - Trial shows safety of drugs for irregular heartbeat patients undergoing treatment
March 24, 2018 - Penn State psychologists shed light on false memories in older adults
March 24, 2018 - Patients who self-discharge should be viewed more positively, say researchers
March 24, 2018 - Wearable brain scanner enables brain imaging whilst moving
March 24, 2018 - Trump Signs $1.3 Trillion Spending Bill, Averts Shutdown
March 24, 2018 - Two drugs prevent heart problems in breast cancer patients
March 24, 2018 - Research provides better understanding of how some cancer cells resist treatment
March 24, 2018 - Certain nutrients found in food may help reduce symptoms of psychotic illness
March 24, 2018 - AbbVie Announces Positive Topline Results from Second Phase 3 Study Evaluating Investigational Elagolix in Women with Uterine Fibroids
March 24, 2018 - AHRQ Is in Trouble | Medpage Today
March 24, 2018 - Could a pap test spot more than just cervical cancer?
March 24, 2018 - Men have greater hospital readmission risk following firearm injury, study shows
March 24, 2018 - Pediatric psychologist shares 11 warning signs of childhood depression
March 24, 2018 - OncoBreak: ‘I Was Normal Once’; Ending Cervical Cancer; Mammo Controversy
March 24, 2018 - Gum Disease by the Numbers
March 24, 2018 - Studies show tool can identify individual needs, supports to help youths with autism, intellectual disabilities
March 24, 2018 - Study reveals cause of extreme nausea in pregnancy
March 24, 2018 - New findings highlight need to reconsider cervical cancer screening guidelines
March 24, 2018 - Smartwatch App Might Help Detect A-Fib
March 24, 2018 - TAVR Reasonable for Low-Flow, Low-Gradient Aortic Stenosis
March 24, 2018 - Kids with severe brain injuries may develop ADHD: study
March 24, 2018 - Researchers explore ways to help older adults taper off and stop using sedatives
March 24, 2018 - Back pain being mismanaged globally
March 24, 2018 - Fingerprint test accurately and noninvasively detects heroin, cocaine users
March 24, 2018 - Leading experts to promote cardiovascular health at EuroPrevent 2018
March 24, 2018 - A Role for Rituximab in Lupus?
March 24, 2018 - New osteoarthritis genes discovered
March 24, 2018 - Maternal intake of DHA supplement linked to higher fat-free body mass in children
March 24, 2018 - Royal College of Pathologists‘ bulletin provides summary of Tissue Handling Workshop
March 24, 2018 - Maternal alcohol use early in pregnancy may be risk factor for infant abdominal malformation
March 24, 2018 - Savara Initiates Phase 2a Clinical Study of Molgradex for the Treatment of NTM Lung Infection
March 24, 2018 - Accelerated WBI Should be the Norm for Most Breast Cancers
March 24, 2018 - Experts seek to standardize treatments for childhood rheumatic diseases
March 24, 2018 - Foil-based measuring chip rapidly detects Legionella
March 24, 2018 - Bariatric surgery linked to positive outcomes in very obese adolescents with type 2 diabetes
March 24, 2018 - Researchers identify chemical responsible for carcinogen formation in recycled wastewater
March 24, 2018 - Obesity and severe obesity continue to rise among U.S. adults
March 24, 2018 - Missed hospital appointments increase after spring clock change in the UK
March 24, 2018 - Researchers explore ways to manage and prevent falls in older adults with dementia
March 24, 2018 - Are there risks from secondhand marijuana smoke? Early science says yes.
March 24, 2018 - NUST MISIS researchers produce elastic metal rods for scoliosis treatment
March 24, 2018 - New University of Bath project seeks to make injections safer
March 24, 2018 - Higher-dose RT does not improve survival but reduces recurrence risk for prostate cancer patients
March 24, 2018 - Researchers examine link between knee pain and depression in older adults
March 24, 2018 - FDA Alert: BD Vacutainer Blood Collection Tubes by Becton, Dickinson and Company (BD): Class I Recall
March 24, 2018 - Daytime Sleepiness Linked to Amyloid Accumulation Without Dementia
March 24, 2018 - Energy storehouses in the brain may be source of Alzheimer’s, targets of new therapy
March 24, 2018 - Praising people with autism shows promise for producing more exercise
March 24, 2018 - Using harmless red or infrared light to diagnose breast cancer
March 24, 2018 - Clash over abortion hobbles a health bill. Again. Here’s how.
March 23, 2018 - Virtual nature environment could be new way to recover from stress
March 23, 2018 - New study identifies key cellular mechanisms behind vascular aging in mice
March 23, 2018 - Nightmares Common Among U.S. Troops, But Seldom Reported
March 23, 2018 - Another Record Low for Tuberculosis in U.S.
March 23, 2018 - Changes in the eye connected to a decline in memory
March 23, 2018 - Radiologist creates dramatic teaching tool using power of VR
March 23, 2018 - Grilled meat could be raising the risk of hypertension finds study
March 23, 2018 - Mutations found in bassoon gene may help explain cause of rare brain disorder
March 23, 2018 - Childhood Brain Injuries May be Linked to ADHD Years Later
March 23, 2018 - Why treating addiction with medication should be carefully considered
March 23, 2018 - Researchers make key discovery about cellular pathway linked to myriad of diseases
March 23, 2018 - Researchers uncover cause of rare childhood neurodegenerative disease
March 23, 2018 - Measles infection in early childhood could contribute to later COPD
March 23, 2018 - Opioid painkiller is top prescription in 11 states
March 23, 2018 - Sienna Biopharmaceuticals Announces First Patient Dosed In Proof-of-Concept Trial of Topical By Design™ JAK Inhibitor SNA-125 for Atopic Dermatitis
March 23, 2018 - In Teen Girls, Neural Patterns May Drive Emotional Resilience
March 23, 2018 - Gene-based test for urine detects, monitors bladder cancer
March 23, 2018 - BD to introduce new digital solution for IV chemotherapy administration process at EAHP 2018
March 23, 2018 - New computational method helps to identify tumor cell mutations with greater accuracy
March 23, 2018 - Researchers identify potential obesity treatment in freezing hunger-signaling nerve
March 23, 2018 - Wales participates in the 100,000 Genomes Project
March 23, 2018 - 24-Hr Paging Cuts ED Visits for Kids with Endocrine Issues
March 23, 2018 - The brain learns completely differently than we’ve assumed since the 20th century
March 23, 2018 - Less nutritious diet mainly contributes to Type 2 diabetes among U.S.-based South Asians
March 23, 2018 - Stony Brook Medicine expert provides tips for healthy diet to decrease cancer risk
March 23, 2018 - New findings could have revolutionary impact on quality of life of older people
March 23, 2018 - Restoring enzyme may help reverse effects of vascular aging, study shows
New techniques give blood biopsies greater promise

New techniques give blood biopsies greater promise

image_pdfDownload PDFimage_print
Killer T cells surround a cancer cell. Credit: NIH

Researchers at the Broad Institute of MIT and Harvard, Koch Institute at MIT, Dana-Farber Cancer Institute, and Massachusetts General Hospital have developed an accurate, scalable approach for monitoring cancer DNA from blood samples.

Reporting in Nature Communications, the team demonstrates that nearly 90 percent of a tumor’s genetic features can be detected in blood samples using whole-exome sequencing, and that the method can be effectively applied in up to 49 percent of patients with advanced cancer—a number likely to increase as sequencing becomes cheaper. This less-invasive tumor sampling, as a window into the cancer’s genome, has a range of potential applications.

“Our ultimate hope is to use blood biopsies to exhaustively search for and characterize even the smallest remnants of tumors,” explained Viktor Adalsteinsson, co-first author on the paper and group leader at the Broad Institute, where he leads the Blood Biopsy Team. “And, as tumors evolve in more advanced stages of cancer, developing resistance or becoming metastatic, we might access timepoints that could be pivotal in deciding which therapies are right for that patient.”

This ability to detect and analyze cancer DNA from a patient’s blood sample is emerging as a promising alternative to invasive surgical biopsies, which can be difficult, painful, and costly—especially when tumors have appeared in locations that are challenging to access.

Blood biopsies (also called liquid biopsies) are poised to overcome many of these issues. They have the potential to allow doctors to track the progress of disease and treatment in real-time and to help researchers understand how tumors resist treatment with far greater resolution.

Understanding cancer without invasive procedures

Cells in the body, including tumor cells, regularly expel fragments of DNA into the bloodstream when they die. With blood biopsies, clinicians collect this “cell-free” DNA from a blood draw and then detect and comprehensively profile the fragments originating from cancer cells. Tracking this data could make it possible to monitor cancer recurrence, a patient’s response to treatment, and other clinically important features, all from blood samples.

The research and development arena for blood biopsies is frequented by both academic and industry players, but with scalable whole-exome sequencing, a team led by Adalsteinsson and colleagues Gavin Ha, Sam Freeman, Matthew Meyerson, J. Christopher Love, and Gad Getz is taking the field in a new and innovative direction.

Compiling a whole exome from DNA fragments currently requires at least 10 percent tumor DNA in a blood sample, but the fraction of tumor DNA in the blood can vary wildly from patient to patient. Because of this variation, the team first desired an unbiased approach for detecting and measuring levels of cancer DNA before attempting whole-exome sequencing.

Across the field, many blood biopsy methods detect tumor DNA by screening for mutations in known cancer-related genes, but this targeted sequencing misses cancers without those mutations.

Co-first author Ha, a postdoctoral scholar at the Broad Institute and Dana-Farber Cancer Institute (DFCI), led the development of a tool called ichorCNA that can analyze DNA fragments for mutation patterns nearly universal in cancer genomes, and as a result capture cancers with both known and unknown mutations. Ha focused on detecting stretches of DNA that have either fewer or greater copies in cancer cells, in contrast to healthy cells.

The research team tested and refined ichorCNA on 1,439 blood samples collected prospectively from 520 metastatic breast or prostate cancer patients at DFCI (a significant effort championed by medical oncologists Atish Choudhury, Daniel Stover, Heather Parsons, Nikhil Wagle, and colleagues).

Using this approach, the researchers found that in 33 to 49 percent of the metastatic breast and prostate cancer patients, depending upon whether one or multiple blood samples were examined, tumor DNA made up greater than 10 percent of the cell-free DNA in their blood—enough to make whole-exome sequencing of cell-free DNA feasible.

Then, to determine whether this sequencing of cell-free tumor DNA could offer the same level of insight into cancer genetics as a tissue biopsy could, the team compared surgically obtained tumor biopsies to data collected from whole-exome sequencing of cell-free DNA from a group of 41 patients. The researchers found that genetic data from blood whole-exome sequencing and tissue biopsies matched significantly across a number of genetic features, such as clonal somatic mutations (88 percent match) and copy number alterations (80 percent match).

These results support cell-free DNA whole-exome sequencing, from blood samples, as a potential substitute for metastatic tumor biopsy sequencing for many patients.

“Our study has demonstrated that we can get a cancer whole exome reliably, from blood; that it reflects the matched tumor biopsy; and that it can be done for a significant fraction of patients with metastatic cancer,” said Adalsteinsson. “This validation suggests that we can use blood biopsies for large-scale genomic characterization of disease in patients with metastatic cancer.”

“It unlocks the potential for a lot of studies that we couldn’t do before,” added Getz, institute member and director of the Cancer Genome Computational Analysis group at Broad and associate professor of Pathology and director of Bioinformatics at the Massachusetts General Hospital Cancer Center and Department of Pathology. “The technology will allow us to track the dynamics of cancer and understand the evolution of drug resistance, or the development of the metastatic state, in a way that isn’t possible through surgical biopsies.”

The new study improves the analysis pipeline for blood biopsies and allows it to be performed at expanded scale. The researchers are actively applying their work to thousands of patients with metastatic cancer who may otherwise not have their tumors biopsied.

“With this work, we now have a framework for the precise measurement and quality control of tumor DNA in the plasma, enabling the genomic analysis of blood biopsies with high technical accuracy,” explained Meyerson, institute member at Broad and professor of pathology at DFCI and Harvard Medical School.

Method is already in use with patients for cancer research

On the back of the team’s success, ichorCNA and subsequent whole-exome sequencing of cell-free DNA have been incorporated into a collaboration with the Broad Institute Genomics Platform to enable comprehensive mapping of metastatic and drug-resistant tumors from blood samples at scale. This approach has also been integrated into direct-to-patient research efforts underway at Broad, including the Metastatic Breast Cancer (MBC) Project, a patient outreach effort that collects saliva and tissue samples—and now blood samples—donated from metastatic breast cancer patients for DNA sequencing to further therapeutic research. Similar efforts to incorporate blood biopsies are underway in the Angiosarcoma Project and upcoming Metastatic Prostate Cancer Project.

“We are excited about using blood biopsies to understand metastatic breast cancer, drug resistance, and tumor evolution, and to get a snapshot of the metastatic setting in patients who might not have available tissue from a metastatic biopsy,” said Nikhil Wagle, an associate member at the Broad Institute, deputy director of the Center for Cancer Precision Medicine at DFCI, and leader of the MBC Project. “With the Blood Biopsy Team’s latest results, it was clear that this technology had reached the right point for us to incorporate into the Metastatic Breast Cancer project.”

A means to perform large-scale blood biopsies could allow researchers and clinicians easy access to the cancer genome, with exciting implications for the way physicians monitor response to treatment, watch for recurrence, and more. The ability to frequently and non-invasively monitor cancer and its treatment could alter clinical trials, increase the resolution with which clinicians understand metastatic cancer, and potentially increase accessibility to quality precision medicine approaches.

“Using cell-free DNA to track cancer is not a new idea, but we’re developing the tools to understand how we can better qualify materials for those types of analyses, and we’re doing it in a way that allows us to look across the genome broadly,” said Love, a Broad associate member, associate professor of chemical engineering at MIT, and a member of the Koch Institute for Integrative Cancer Research at MIT. “We’ve established quality metrics to make sure that this technology is cost-effective and scalable for thousands of patients and samples a year.”

Explore further:
Genetic alterations in treatment-resistant metastatic breast cancer found to be distinct from those in primary tumors

More information:
Viktor A. Adalsteinsson et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors, Nature Communications (2017). DOI: 10.1038/s41467-017-00965-y

Journal reference:
Nature Communications

Provided by:
Broad Institute of MIT and Harvard

Tagged with:

About author

Related Articles