Cyclin D1, a novel molecular marker of minimal residual disease, in metastatic neuroblastoma Journal Article
| Authors: | Cheung, I. Y.; Feng, Y.; Vickers, A.; Gerald, W.; Cheung, N. K. V. |
| Article Title: | Cyclin D1, a novel molecular marker of minimal residual disease, in metastatic neuroblastoma |
| Abstract: | Accurate monitoring of minimal residual disease (MRD) is critical for the management of metastatic neuroblastoma (NB). We evaluated cyclin D1 (CCND1), a cell-cycle control gene, as a novel MRD marker of NB. Using quantitative reverse transcriptase-polymerase chain reaction, we studied CCND1 expression in 133 solid tumors of different histological types, including 39 NB tumors, and examined its potential clinical utility as an early response marker in the bone marrows before and after treatment of 118 stage 4 patients enrolled after induction chemotherapy in an immunotherapy protocol. Based on 40 normal marrow and peripheral blood samples, a CCND1 transcript value greater than the mean + 2 SD was defined as positive. Sensitivity of this assay was one NB cell in 106 normal mononuclear cells. CCND1 transcript levels were high in NB, breast cancer, and Ewing family tumors. Among the NB patients evaluated, early (2.5 months from protocol entry) marrow response was strongly associated with both progression-free (P = 0.0001) and overall survival (P = 0.0006). CCND1 response remained predictive of survival among a subset of 66 patients who had no histological evidence of marrow disease before immunotherapy. We conclude that CCND1 has potential clinical utility as a novel molecular marker of MRD in the bone marrow of patients with metastatic NB. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology. |
| Keywords: | controlled study; human tissue; human cell; major clinical study; overall survival; genetics; histopathology; disease free survival; cancer staging; antineoplastic agent; neoplasm staging; sensitivity analysis; accuracy; metabolism; cancer immunotherapy; metastasis; reverse transcription polymerase chain reaction; multiple cycle treatment; breast cancer; gene expression profiling; bone marrow; granulocyte macrophage colony stimulating factor; tumor markers, biological; patient monitoring; tumor marker; prediction; monoclonal antibody; ewing sarcoma; kaplan-meiers estimate; gene expression regulation; patient care; gene expression regulation, neoplastic; immunotherapy; mononuclear cell; neuroblastoma; messenger rna; blood sampling; minimal residual disease; neuroblastoma cell; neoplasm, residual; rna, messenger; quantitative analysis; nucleotide sequence; neoplasm metastasis; cell count; kaplan meier method; cyclin d1; cell cycle regulation; genetic screening; cucurbita |
| Journal Title: | Journal of Molecular Diagnostics |
| Volume: | 9 |
| Issue: | 2 |
| ISSN: | 1525-1578 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2007-04-01 |
| Start Page: | 237 |
| End Page: | 241 |
| Language: | English |
| DOI: | 10.2353/jmoldx.2007.060130 |
| PUBMED: | 17384216 |
| PROVIDER: | scopus |
| PMCID: | PMC1867438 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 17 November 2011" - "CODEN: JMDIF" - "Molecular Sequence Numbers: GENBANK: NM_002046, NM_053056;" - "Source: Scopus" |
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