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Clin Cancer Res. 2017 Sep 15;23(18):5374-5383. doi: 10.1158/1078-0432.CCR-16-2647. Epub 2017 May 30.

Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

Author information

1
Department of Pediatrics, Keck School of Medicine, University of Southern California, Children's Center for Cancer and Blood Diseases, Los Angeles, California. amarachelian@chla.usc.edu.
2
Children's Hospital Los Angeles, Los Angeles, California.
3
Department of Pediatrics, Keck School of Medicine, University of Southern California, Children's Center for Cancer and Blood Diseases, Los Angeles, California.
4
Department of Radiology, Keck School of Medicine, University of Southern California, Children's Center for Cancer and Blood Diseases, Los Angeles, California.
5
Department of Pathology, Keck School of Medicine, University of Southern California, Children's Center for Cancer and Blood Diseases, Los Angeles, California.
6
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
7
Aflac Cancer Center, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.
8
Cook Children's Health Care System, Fort Worth, Texas.
9
University of California, San Francisco Children's Hospital, San Francisco, California.
10
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Children's Center for Cancer and Blood Diseases, Los Angeles, California.

Abstract

Purpose: We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma.Experimental Design: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, ΔCt, for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, 123I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between ΔCt and progression-free survival (PFS).Results: NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their ΔCt values were correlated (Spearman r = 0.67, P < 0.0001), although bone marrow Ct was 7.9 ± 0.5 Ct stronger than blood Ct When bone marrow morphology, MIBG, or CT/MRI were positive, NB-mRNA was detected in 99% (99/100), 88% (100/113), and 81% (82/101) of bone marrow samples. When all three were negative, NB-mRNA was detected in 55% (11/20) of bone marrow samples. Bone marrow NB-mRNA correlated with bone marrow morphology or MIBG positivity (P < 0.0001 and P = 0.007). Bone marrow and blood ΔCt values correlated with PFS (P < 0.001; P = 0.001) even when bone marrow was morphologically negative (P = 0.001; P = 0.014). Multivariate analysis showed that bone marrow and blood ΔCt values were associated with PFS independently of clinical disease and MYCN gene status (P < 0.001; P = 0.055).Conclusions: This five-gene NB5 assay for NB-mRNA improves definition of disease status and correlates independently with PFS in relapsed/refractory neuroblastoma. Clin Cancer Res; 23(18); 5374-83. ©2017 AACR.

PMID:
28559462
DOI:
10.1158/1078-0432.CCR-16-2647
[Indexed for MEDLINE]
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