Quantitative polymerase chain reaction analysis with allele-specific oligonucleotide primers for individual IgH VDJ regions to evaluate tumor burden in myeloma patients

Sata, Hiroshi; Shibayama, Hirohiko; Maeda, Ichiro; Habuchi, Yoko; Nakatani, Eiji; Fukushima, Kentaro; Fujita, Jiro; Ezoe, Sachiko; Tadokoro, Seiji; Maeda, Takeyasu; Mizuki, Masao; Kosugi, Satoru; Nakagawa, Masashi; Ueda, Shuji; Iida, Masato; Tokumine, Yukihiro; Azenishi, Yasuhiko; Matsui, Hideki; Oritani, Kenji

doi:10.1016/j.exphem.2015.01.002

Cited by 14 publications

(15 citation statements)

References 24 publications

(31 reference statements)

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“…ASO‐qPCR is a powerful method for MRD evaluation with sensitivity comparable to other methods . The sensitivity of our assay reached 10 −4 ‐10 −6 and corresponds to sensitivities described by other studies . However, applicability of ASO‐qPCR is often limited by technical complexity and variety of technical problems .…”

Section: Discussionsupporting

confidence: 74%

“…Here, we performed a long-term comprehensive study of cfDNA dynamics, which extends previous findings about applicability of cfDNA analysis for minimally invasive testing of MM patients. 30,31 Our results show that levels of tumor-specific cfDNA drop in response to therapy. Both, the induction therapy and ASCT signifi- A study on more than 1000 individuals indicated that more gradual response (time to plateau >120 days) of MM patients is connected to longer survival compared with rapid responders.…”

Section: Discussionmentioning

confidence: 67%

“…Analysis of tumor-specific cfDNA is a promising, emerging form of liquid biopsy in hematological malignancies. 26 So far, several studies investigated cfDNA in MM patients, [27][28][29][30] but only limited long-term data are available. Here, we performed a long-term comprehensive study of cfDNA dynamics, which extends previous findings about applicability of cfDNA analysis for minimally invasive testing of MM patients.…”

Section: Discussionmentioning

confidence: 99%

“…35,36 The sensitivity of our assay reached 10 −4 -10 −6 and corresponds to sensitivities described by other studies. 30,37 However, applicability of ASO-qPCR is often limited by technical complexity and variety of technical problems. 38 In our study, lower applicability mirrors in the number of analyzed vs. enrolled patients (45/112) with main reason for exclusion being the inability to identify patient-specific VDJ rearrangement (see Appendix S1 for details).…”

Section: Discussionmentioning

confidence: 99%

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Dynamics of tumor‐specific cfDNA in response to therapy in multiple myeloma patients

Vrábel

Sedlaříková

Besse

et al. 2019

European J of Haematology

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Objectives Progress in multiple myeloma treatment allows patients to achieve deeper responses, for which the assessment of minimal residual disease (MRD) is critical. Typically, bone marrow samples are used for this purpose; however, this approach is site‐limited. Liquid biopsy represents a minimally invasive and more comprehensive technique that is not site‐limited, but equally challenging. Methods While majority of current data comes from short‐term studies, we present a long‐term study on blood‐based MRD monitoring using tumor‐specific cell‐free DNA detection by ASO‐qPCR. One hundred and twelve patients were enrolled into the study, but long‐term sampling and analysis were feasible only in 45 patients. Results We found a significant correlation of quantity of tumor‐specific cell‐free DNA levels with clinically meaningful events [induction therapy (P = .004); ASCT (P = .012)]. Moreover, length of cfDNA fragments is associated with better treatment response of patients. Conclusions These results support the concept of tumor‐specific cell‐free DNA as a prognostic marker.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Dynamics of tumor‐specific cfDNA in response to therapy in multiple myeloma patients

Vrábel

Sedlaříková

Besse

et al. 2019

European J of Haematology

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“…quantified ASO‐PCR products from peripheral blood mononuclear cells (PBMNC), BM mononuclear cells (BMMNC) and CD20 + CD38 − B‐cell population in BM. They also quantified cfDNA from sera to check the presence of these fragments in PB . This study was quite small, analyzing only 30 MM patients of which 23 were followed and only 20 quantified.…”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

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Although tumor cells are the most reliable source of tumor DNA, biopsy of the tumor is an invasive procedure that should be avoided in some cases. The main limitation of any biopsy is sampling of one tumor site, which may not represent all malignant clones due to the heterogeneity of the tumor. These clones respond to treatment differently and thus directly influence survival of the patient. Circulating cell-free DNA (cfDNA) is released from multiple tumor sites, reflects overall heterogeneity of the tumor, and correlates with its progression. Detection of tumor-specific genetic and epigenetic aberrations in cfDNA could have a direct impact on molecular diagnosis, prognosis, follow-up of disease, monitoring of minimal residual disease, and response to treatment. While most cfDNA data are still experimental, they are very promising. This review focuses on cfDNA in hematological malignancies. K E Y W O R D Sacute lymphoblastic leukemia, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes | INTRODUCTION AND HISTORYIn recent years, significant advances in diagnosis and treatment of cancer have been made. Nevertheless, invasive and painful procedures, such as tissue or bone marrow (BM) biopsy, are gold standard for disease diagnosis and monitoring. At the same time, they should be avoided in some cases-if BM is fibrotic or tumor tissue is not easily accessible.1 As a single tumor site is sampled during BM biopsy, it may not contain all malignant clones. 2,3 As these clones react to treatment differently, they directly influence survival of patients; thus, easily accessible markers that would mirror the entire heterogeneity of the tumor are sought after. Such putative markers are present in peripheral blood (PB), for example, circulating tumor cells (CTC) or circulating nucleic acids. 3,4 Biopsies of PB-the so-called liquid biopsies-are at the center of attention of researchers as well as clinicians and represent a newer and more comprehensive approach to obtain tumor information. Analysis of circulating molecules (microRNA, cell-free DNA, and others) as well as CTC might describe the tumor in more detail.Cell-free DNA (cfDNA) is one of these possibilities.CfDNA is formed by DNA fragments. These fragments are gathered from all tumor sites into circulation; thus, they mirror the complexity and heterogeneity of the entire tumor. 3 CfDNA may serve as an excellent diagnostic marker as it reflects the disease in more detail than existing biomarkers. Moreover, because of easy access, cfDNA sampling is suitable for repeated analyses. 4 As it correlates with disease progression, it could serve as a prognostic marker as well. 5,6The first reference of cfDNA dates back to 1948. In that year, CfDNA may shortly become such a marker. | CHARACTERISTICS OF CFDNAMolecules of cfDNA are extracellular fragments of short doublestranded DNA found in PB and other body fluids, for example, in urine, saliva, breast milk, and synovial fluid. 16,17 Generally, cfDNA is found in very low concentrations in PB of HD (10-100...

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Hematologic Malignancy Biomarkers in Proximal Fluids

Dakubo

2019

Cancer Biomarkers in Body Fluids

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Quantitative polymerase chain reaction analysis with allele-specific oligonucleotide primers for individual IgH VDJ regions to evaluate tumor burden in myeloma patients

Cited by 14 publications

References 24 publications

Dynamics of tumor‐specific cfDNA in response to therapy in multiple myeloma patients

Dynamics of tumor‐specific cfDNA in response to therapy in multiple myeloma patients

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Hematologic Malignancy Biomarkers in Proximal Fluids

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