Liquid biopsies have generated a lot of excitement in cancer care because they are a noninvasive alternative to standard tissue biopsy. Both circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are important types of liquid biopsy, but they are rarely analyzed together.
Findings from a new study suggest that CTCs and cfDNA may be used interchangeably for comprehensive genomic profiling in multiple myeloma. Also, using them together can potentially widen the applicability of liquid biopsies for multiple myeloma patients, with the hope that they could in the future replace the need for the painful bone marrow biopsies that are currently used to monitor disease.
The study was published online April 27 in Nature Communications.
Senior author Irene Ghobrial, MD, a medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, explained that they are hoping to bring blood biopsy into the clinical setting, “but we are not there yet. We are working hard on making it available for patients, and we are hoping that will happen in a couple of years.”
She told Medscape Medical News that either CTCs or cfDNA can be used. “Both of them give us good information, but this is the first time that we looked at them comparatively,” she said. “We can use one or the other.”
The fact that findings from both methods are commensurate with each other at a comprehensive level makes genetic profiling of tumors from blood feasible.
In this study, results were comparable to those of bone marrow biopsy. “Right now they are not replacing regular biopsy, but the hope is that if we do a large enough study proving that it can indeed can replace bone marrow biopsy, then it will in the future,” said Ghobrial.
High Concordance Observed
The authors explain that multiple myeloma evolves from premalignant stages to symptomatic disease. It is currently incurable, owing to intrinsic and acquired therapeutic resistance. Improved modalities are needed to track clonal evolution to assist in clinical management.
The team first used ultra-low-pass whole-genome sequencing, a rapid screening method, and combined it with ichorCNA, a cost-effective approach that the team had recently developed to estimate tumor fraction in cfDNA. Using both techniques, they were able to estimate the tumor fraction in cfDNA from 107 patients and CD138-selected pools of CTCs from 56 patients.
Analyzing both CTCs and cfDNA led to finding a higher fraction of patients having at least one sample with sufficient tumor content (≥5% to 10%) for whole-genome sequencing, which was then performed on 24 samples that included matched cfDNA and bone marrow biopsy specimens from nine patients along with matched cfDNA, CTCs, and bone marrow biopsy specimens from an additional four patients.
Overall, there was a high concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies.
“Our data indicate that sequencing of both cfDNA and CTCs could capture the mutational landscape of bone marrow tumors and provide a comprehensive profile of clonal heterogeneity in multiple myeloma,” the authors write. In turn, this will enable noninvasive profiling of tumor evolution using liquid biopsies.
These results must now be confirmed in larger patient cohorts, which are currently ongoing. Moving forward, Ghobrial and her team plan to develop methods that provide more detailed and clinically appropriate genetic information 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,” said co–first author Jihye Park, PhD, a researcher in the Ghobrial laboratory at Dana Farber, in a statement.
The study was funded by the National Cancer Institute, the Multiple Myeloma Research Foundation, the Leukemia and Lymphoma Society, and the Gerstner Family Foundation. The authors have disclosed no relevant financial relationships.
Nat Commun.Published online April 27, 2018. Full text
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