Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes

Yasuhiro Suzuki, Akihiro Tomita, Fumika Nakamura, Chisako Iriyama, Mizuho Shirahata-Adachi, Kazuyuki Shimada, Akimi Akashi, Yuichi Ishikawa, Norio Kaneda, Hitoshi Kiyoi

Research output: Contribution to journalArticle

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Abstract

Genetic alterations in myelodysplastic syndromes (MDS) are critical for pathogenesis. We previously showed that peripheral blood cell-free DNA (PBcfDNA) may be more sensitive for genetic/epigenetic analyses than whole bone marrow (BM) cells and mononuclear cells in peripheral blood (PB). Here we analyzed the detailed features of PBcfDNA and its utility in genetic analyses in MDS. The plasma-PBcfDNA concentration in MDS and related diseases (N = 33) was significantly higher than that in healthy donors (N = 14; P = 0.041) and in International Prognostic Scoring System higher-risk groups than that in lower-risk groups (P = 0.034). The concentration of plasma-/serum-PBcfDNA was significantly correlated with the serum lactate dehydrogenase level (both P < 0.0001) and the blast cell count in PB (P = 0.034 and 0.025, respectively). One nanogram of PBcfDNA was sufficient for one assay of Sanger sequencing using optimized primer sets to amplify approximately 160-bp PCR products. PBcfDNA (approximately 50 ng) can also be utilized for targeted sequencing. Almost all mutations detected in BM-DNA were also detected using corresponding PBcfDNA. Analyses using serially harvested PBcfDNA from an RAEB-2 patient showed that the somatic mutations and a single nucleotide polymorphism that were detected before allogeneic transplantation were undetectable after transplantation, indicating that PBcfDNA likely comes from MDS clones that reflect the disease status. PBcfDNA may be a safer and easier alternative to obtain tumor DNA in MDS.

Original languageEnglish
Pages (from-to)1329-1337
Number of pages9
JournalCancer Science
Volume107
Issue number9
DOIs
Publication statusPublished - 01-09-2016

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Myelodysplastic Syndromes
Blood Cells
DNA
Neoplasms
Refractory Anemia with Excess of Blasts
Mutation
Homologous Transplantation
Serum
L-Lactate Dehydrogenase
Epigenomics
Bone Marrow Cells
Single Nucleotide Polymorphism
Clone Cells
Cell Count
Transplantation
Bone Marrow
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Suzuki, Yasuhiro ; Tomita, Akihiro ; Nakamura, Fumika ; Iriyama, Chisako ; Shirahata-Adachi, Mizuho ; Shimada, Kazuyuki ; Akashi, Akimi ; Ishikawa, Yuichi ; Kaneda, Norio ; Kiyoi, Hitoshi. / Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes. In: Cancer Science. 2016 ; Vol. 107, No. 9. pp. 1329-1337.
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abstract = "Genetic alterations in myelodysplastic syndromes (MDS) are critical for pathogenesis. We previously showed that peripheral blood cell-free DNA (PBcfDNA) may be more sensitive for genetic/epigenetic analyses than whole bone marrow (BM) cells and mononuclear cells in peripheral blood (PB). Here we analyzed the detailed features of PBcfDNA and its utility in genetic analyses in MDS. The plasma-PBcfDNA concentration in MDS and related diseases (N = 33) was significantly higher than that in healthy donors (N = 14; P = 0.041) and in International Prognostic Scoring System higher-risk groups than that in lower-risk groups (P = 0.034). The concentration of plasma-/serum-PBcfDNA was significantly correlated with the serum lactate dehydrogenase level (both P < 0.0001) and the blast cell count in PB (P = 0.034 and 0.025, respectively). One nanogram of PBcfDNA was sufficient for one assay of Sanger sequencing using optimized primer sets to amplify approximately 160-bp PCR products. PBcfDNA (approximately 50 ng) can also be utilized for targeted sequencing. Almost all mutations detected in BM-DNA were also detected using corresponding PBcfDNA. Analyses using serially harvested PBcfDNA from an RAEB-2 patient showed that the somatic mutations and a single nucleotide polymorphism that were detected before allogeneic transplantation were undetectable after transplantation, indicating that PBcfDNA likely comes from MDS clones that reflect the disease status. PBcfDNA may be a safer and easier alternative to obtain tumor DNA in MDS.",
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Suzuki, Y, Tomita, A, Nakamura, F, Iriyama, C, Shirahata-Adachi, M, Shimada, K, Akashi, A, Ishikawa, Y, Kaneda, N & Kiyoi, H 2016, 'Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes', Cancer Science, vol. 107, no. 9, pp. 1329-1337. https://doi.org/10.1111/cas.12994

Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes. / Suzuki, Yasuhiro; Tomita, Akihiro; Nakamura, Fumika; Iriyama, Chisako; Shirahata-Adachi, Mizuho; Shimada, Kazuyuki; Akashi, Akimi; Ishikawa, Yuichi; Kaneda, Norio; Kiyoi, Hitoshi.

In: Cancer Science, Vol. 107, No. 9, 01.09.2016, p. 1329-1337.

Research output: Contribution to journalArticle

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T1 - Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes

AU - Suzuki, Yasuhiro

AU - Tomita, Akihiro

AU - Nakamura, Fumika

AU - Iriyama, Chisako

AU - Shirahata-Adachi, Mizuho

AU - Shimada, Kazuyuki

AU - Akashi, Akimi

AU - Ishikawa, Yuichi

AU - Kaneda, Norio

AU - Kiyoi, Hitoshi

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