Minimal residual disease monitoring in neuroblastoma patients based on the expression of a set of real-time RT-PCR markers in tumor-initiating cells

Hartomo,Tri  Budi; Kozaki,Aiko; Hasegawa,Daiichiro; Pham,Thi  Van Huyen; Yamamoto,Nobuyuki; Saitoh,Atsuro; Ishida,Toshiaki; Kawasaki,Keiichiro; Kosaka,Yoshiyuki; Ohashi,Hiroki; Yamamoto,Tomoto; Morikawa,Satoru; Hirase,Satoshi; Kubokawa,Ikuko; Mori,Takeshi; Yanai,Tomoko; Hayakawa,Akira; Takeshima,Yasuhiro; Iijima,Kazumoto; Matsuo,Masafumi; Nishio,Hisahide; Nishimura,Noriyuki

doi:10.3892/or.2013.2286

April 2013 Volume 29 Issue 4

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April 2013 Volume 29 Issue 4

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Article

Minimal residual disease monitoring in neuroblastoma patients based on the expression of a set of real-time RT-PCR markers in tumor-initiating cells

Authors:
- Tri Budi Hartomo
- Aiko Kozaki
- Daiichiro Hasegawa
- Thi Van Huyen Pham
- Nobuyuki Yamamoto
- Atsuro Saitoh
- Toshiaki Ishida
- Keiichiro Kawasaki
- Yoshiyuki Kosaka
- Hiroki Ohashi
- Tomoto Yamamoto
- Satoru Morikawa
- Satoshi Hirase
- Ikuko Kubokawa
- Takeshi Mori
- Tomoko Yanai
- Akira Hayakawa
- Yasuhiro Takeshima
- Kazumoto Iijima
- Masafumi Matsuo
- Hisahide Nishio
- Noriyuki Nishimura
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Affiliations: Department of Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan, Department of Hematology and Oncology, Kobe Children's Hospital, Kobe, Japan, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan, Department of Medical Rehabilitation, Kobe Gakuin University, Kobe, Japan
Pages: 1629-1636
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Published online on: February 12, 2013

https://doi.org/10.3892/or.2013.2286
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Abstract

Minimal residual disease (MRD) is derived from tumor-initiating cells (TICs) and is responsible for tumor relapse. Neuroblastoma is characterized by extreme tumor heterogeneity, and more than half of high-risk patients experience tumor relapse. To overcome tumor heterogeneity and achieve more sensitive detection of MRD, several sets of real-time RT-PCR markers have been reported for MRD monitoring in neuroblastoma patients from different centers. However, these markers vary across centers and are still being validated. In the present study, we validated the ability of 14 commonly used real-time RT-PCR markers to detect MRD based on their expression in neuroblastoma TICs, and we developed a novel MRD detection protocol, which scored the samples as MRD-positive when the expression of one of the 11 real-time RT-PCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) exceeded the normal range. By using this protocol, we prospectively monitored MRD in 73 bone marrow (BM), 12 peripheral blood stem cell and 8 peripheral blood samples from 14 neuroblastoma patients treated at a single center. We scored 100, 56, 56 and 57% BM cytology-positive, elevated vanillylmandelic acid (VMA), elevated homovanillic acid (HVA) and elevated neuron-specific enolase (NSE) samples as MRD-positive, respectively. MRD was also positive in 48, 45, 46 and 43% of the BM cytology-negative and normal VMA, normal HVA and normal NSE samples, respectively. These results suggest that the present MRD detection protocol based on the expression of a set of 11 real-time RT-PCR markers in neuroblastoma TICs achieves sensitive MRD monitoring in neuroblastoma patients.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Minimal residual disease monitoring in neuroblastoma patients based on the expression of a set of real-time RT-PCR markers in tumor-initiating cells

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