Exploiting gene expression profiling to identify novel minimal residual disease markers of neuroblastoma Journal Article


Authors: Cheung, I. Y.; Feng, Y.; Gerald, W.; Cheung, N. K. V.
Article Title: Exploiting gene expression profiling to identify novel minimal residual disease markers of neuroblastoma
Abstract: Purpose: Minimal residual disease (MRD) presents a significant hurdle to curing metastatic neuroblastoma. Biological therapies directed against MRD can improve outcome. Evaluating treatment efficacy requires MRD measurement, which serves as surrogate endpoint. Because of tumor heterogeneity, no single marker will likely be adequate. Genome-wide expression profiling can uncover potential MRD markers differentially expressed in tumors over normal marrow/blood. Experimental Design: Gene expression array was carried out on 48 stage 4 tumors and 9 remission marrows using the Affymetrix U95 gene chip. Thirty-four genes with a tumor-tomarrow expression ratio higher than tyrosine hydroxylase were identified. Quantitative reverse transcription-PCR was done on all 34 genes to study the dynamic range of tumor cell detection and the expressionof these genes innormal marrow/blood samples andin stage 4 neuroblastoma tumors.Top ranking markers were then tested for prognostic significance in the marrows of stage 4 patients collected from the same treatment protocol after two cycles of immunotherapy. Results: Based on sensitivity assays, 8 top-ranking markers were identified: CCND1, CRMP1, DDC, GABRB3, ISL1, KIF1A, PHOX2B, and TACC2. They were abundantly expressed in stage IV neuroblastoma tumors (n = 20)a nd had low to no detection in normal marrow/blood samples (n = 20). Moreover, expression of CCND1, DDC, GABRB3, ISL1, KIF1A, and PHOX2B in 116 marrows sampled after two treatment cycles was highly prognostic of progression-free and over-all survival (P < 0.001). Conclusions: Marker discovery based on differential gene expression profiling, stringent sensitivity and specificity assays, and well-annotated patient samples can rapidly prioritize and identify potential MRD markers of neuroblastoma. © 2008 American Association for Cancer Research.
Keywords: cancer survival; controlled study; human tissue; unclassified drug; human cell; genetics; cancer staging; sensitivity and specificity; reverse transcription polymerase chain reaction; gene expression; gene expression profiling; bone marrow; tumor markers, biological; clinical protocol; tumor marker; cancer regression; immunotherapy; evaluation; infant; neuroblastoma; tyrosine 3 monooxygenase; minimal residual disease; neoplasm, residual; microarray analysis; quantitative analysis; nucleotide sequence; tumor cell; genome; homeodomain protein; cyclin d1; 4 aminobutyric acid a receptor; aromatic levo amino acid decarboxylase; collapsin response mediator protein 1; gamma aminobutyric acid a receptor, beta 3; isl lim homeobox 1; kinesin 1; kinesin family member 1a; paired like homeobox 2b
Journal Title: Clinical Cancer Research
Volume: 14
Issue: 21
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2008-11-01
Start Page: 7020
End Page: 7027
Language: English
DOI: 10.1158/1078-0432.ccr-08-0541
PUBMED: 18980998
PROVIDER: scopus
PMCID: PMC2670609
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Molecular Sequence Numbers: GENBANK: AA029437, AA102788, AA167714, AA420624, AB008109, AB011103, AI198311, AI199503, AI377558, AI573279, AI687064, AI857856, AL037611, AL096719, AL120032, AW016235, D45352, D78012, D78014, D82344, L10333, M11433, M17589, M25667, M25756, M76180, U07559, U16954, U38810, U52112, W21875, X04741, X59798, Y00064, Z78388;" - "Source: Scopus"
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MSK Authors
  1. Nai-Kong Cheung
    439 Cheung
  2. William L Gerald
    367 Gerald
  3. Irene Y Cheung
    73 Cheung
  4. Yongqiang Feng
    6 Feng
  5. Yi Feng
    5 Feng