In multiple myeloma, different types of blood biopsies match up well with bone marrow tests

April 27, 2018, Dana-Farber Cancer Institute
Micrograph of a plasmacytoma, the histologic correlate of multiple myeloma. H&E stain. Credit: Wikipedia/CC BY-SA 3.0

Bone marrow biopsies are the gold standard for diagnosing and monitoring the progression of multiple myeloma, but these procedures are far too invasive to perform at every patient visit. Scientists from the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard, however, have shown that two ways to measure multiple myeloma DNA in blood samples provide highly detailed sets of genetic information that agree well not just with each other but with results from bone marrow tests.

"Until now, we haven't had a good way to measure how cell populations evolve from precursor stages to diagnosed disease, and then respond to treatments, says Irene Ghobrial, MD, a Dana-Farber medical oncologist. "This is where biopsies can make a huge difference—extending our understanding of multiple myeloma, and really giving us a timeline of how the disease progresses and responds to therapy."

The collaborative research examined blood biopsies that gathered multiple myeloma tumor DNA from two sources. One is circulating free DNA (cfDNA), scraps of DNA released into the bloodstream by dying cells. The other is circulating tumor cells (CTCs)—myeloma cells themselves.

"Our discovery that cfDNA and CTC analyses agree with each other at the comprehensive level is an important finding, because this means that routine genetic profiling of patient tumors from blood would be feasible," says Ghobrial, co-senior author on a paper reporting the work in Nature Communications.

The blood biopsy analyses followed a two-step sequencing approach, says Viktor Adalsteinsson, PhD, group leader of the Blood Biopsy Team at the Broad Institute and co-senior author on the paper. The first step, developed by his team and called "ultra-low pass" whole genome sequencing, was a cost-effective method to identify with tumor DNA fraction of at least 5-10%, allowing more comprehensive genetic analysis. In the second step, the researchers performed whole exome sequencing (analyzing the protein-coding regions of the genome) on those samples.

The investigators examined cfDNA from 107 patients and CTCs from 56 patients. The scientists then matched up cfDNA with bone marrow data from nine patients, and compared all three forms of biopsy in four additional patients. Overall, the gene profiles overlapped closely—demonstrating about 99% agreement between liquid and bone marrow biopsies for tumor gene mutations, for instance.

Such high levels of agreement suggest that the two forms of liquid biopsy might be used interchangeably to track patients with multiple myeloma, the researchers say, and employing both techniques might further increase the chances of understanding the disease in each patient.

It's also possible that blood biopsies will offer more comprehensive genetic information than bone marrow tests, says Salomon Manier, MD, PhD, co-first author on the paper and a former graduate student in the Ghobrial lab.

Knowing the entire genetic spectrum of disease is crucial to individualize treatment, especially given the growing number of therapeutic options for multiple myeloma, Manier points out. But bone marrow biopsies collect cells from just one location, so those tests can miss nearby cells with quite different characteristics.

"We can't do personalized medicine with a single ," he says. "We need these blood biopsies to help guide treatment, because patients' tumors change over time."

The investigators emphasize that results of their study must be confirmed in larger patient cohorts, now ongoing, before blood biopsies can be brought into clinical use.

Among their next steps, the scientists aim to develop methods that provide more detailed and clinically appropriate , and to hone techniques that work in blood samples with lower fractions of cancer DNA. "Our ultimate goal is to eventually use all the samples to monitor disease progression," says Jihye Park, PhD, researcher in the Ghobrial lab and co-first author on the paper.

"The technology is basically there, says Ghobrial. "Our are so excited to see these tests, and now we need to develop clinical tools that become part of routine testing."

"These noninvasive techniques can really open the door for longitudinal study of cancer evolution and progression," says Adalsteinsson, whose group pursues many projects to comprehensively sequence solid tumors as well as blood cancers. "We believe it's important to look broadly at a patient's cancer genome and how it changes over time—to identify not only the known actionable mutations of today but also to discover new ones that will inform better and more effective treatments of tomorrow."

Explore further: Tracking how multiple myeloma evolves by sequencing DNA in the blood

Related Stories

Tracking how multiple myeloma evolves by sequencing DNA in the blood

December 10, 2017
Although people with multiple myeloma usually respond well to treatment, the blood cancer generally keeps coming back. Following genetic changes in how the disease evolves over time will help to understand the disease and, ...

Sequencing offers clues to progression toward multiple myeloma

December 10, 2017
Researchers at Dana-Farber Cancer Institute have carried out the largest genomic analysis of patients with smoldering multiple myeloma (SMM), a precursor to full-blown blood cancer that doesn't show outward symptoms. The ...

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

Researchers discover 40 genes involved in early development of myeloma

April 9, 2018
Researchers have revealed 40 genes involved in the development of myeloma, increasing our understanding of the complex genetics behind the incurable blood cancer.

Early treatment may prevent progression to multiple myeloma

December 5, 2016
Early intervention with an immunotherapy-based drug combination may prevent progression of high-risk "smoldering" multiple myeloma to the full-blown disease, according to researchers from Dana-Farber Cancer Institute.

'Liquid biopsy' can help predict outcomes in metastatic triple-negative breast cancer

February 16, 2018
A clinically relevant "liquid biopsy" test can be used to profile cancer genomes from blood and predict survival outcomes for patients with metastatic triple negative breast cancer (TNBC), according to new research published ...

Recommended for you

Revealing the molecular mystery of human liver cells

October 22, 2018
A map of the cells in the human liver has been created by University Health Network Transplant Program and University of Toronto researchers, revealing for the first time differences between individual cells at the molecular ...

New tool gives deeper understanding of glioblastoma

October 22, 2018
Researchers in the lab of Charles Danko at the Baker Institute for Animal Health have developed a new tool to study genetic "switches" active in glioblastoma tumors that drive growth of the cancer. In a new paper in Nature ...

RNA thought to spread cancer shows ability to suppress breast cancer metastasis

October 22, 2018
Researchers at The University of Texas MD Anderson Cancer Center have discovered that a form of RNA called metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to suppress breast cancer metastasis in mice, ...

Targeting a hunger hormone to treat obesity

October 22, 2018
About 64 per cent of Canadian adults are overweight or obese, according to Health Canada. That's a problem, because obesity promotes the emergence of chronic diseases such as type 2 diabetes, heart disease and some cancers.

New drug combination destroys chemo-resistant blood cancer

October 22, 2018
Researchers from The Ottawa Hospital and the University of Ottawa have developed a promising targeted strategy to treat chemotherapy-resistant acute myeloid leukemia (AML) and a diagnostic test to determine which AML patients ...

Major trial shows targeted drug extends breast cancer survival

October 22, 2018
Combining a targeted drug with hormone therapy substantially extends survival for women with advanced breast cancer, a major clinical trial has found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.