title: Minimal residual disease monitoring in neuroblastoma patients based             on the expression of a set of real-time RT-PCR markers in tumor-initiating cells.
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.
authors: Department of Epidemiology, Kobe University Graduate School of Medicine, and Department of Hematology and Oncology, Kobe Children's Hospital, Kobe, Japan.
authors: Tri Budi
authors: TB
authors: Hartomo
authors: Aiko
authors: A
authors: Kozaki
authors: Daiichiro
authors: D
authors: Hasegawa
authors: Thi
authors: T
authors: Van Huyen Pham
authors: Nobuyuki
authors: N
authors: Yamamoto
authors: Atsuro
authors: A
authors: Saitoh
authors: Toshiaki
authors: T
authors: Ishida
authors: Keiichiro
authors: K
authors: Kawasaki
authors: Yoshiyuki
authors: Y
authors: Kosaka
authors: Hiroki
authors: H
authors: Ohashi
authors: Tomoto
authors: T
authors: Yamamoto
authors: Satoru
authors: S
authors: Morikawa
authors: Satoshi
authors: S
authors: Hirase
authors: Ikuko
authors: I
authors: Kubokawa
authors: Takeshi
authors: T
authors: Mori
authors: Tomoko
authors: T
authors: Yanai
authors: Akira
authors: A
authors: Hayakawa
authors: Yasuhiro
authors: Y
authors: Takeshima
authors: Kazumoto
authors: K
authors: Iijima
authors: Masafumi
authors: M
authors: Matsuo
authors: Hisahide
authors: H
authors: Nishio
authors: Noriyuki
authors: N
authors: Nishimura
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D006801:Humans; D018365:Neoplasm, Residual / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor