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Reduced Expression of CAMTA1 Correlates with Adverse Outcome in Neuroblastoma Patients

Authors' Affiliations: Departments of ¹ Tumour Genetics B030, ² Molecular Genetics B060, ³ Theoretical Bioinformatics B080, and ⁴ Central Unit Biostatistics, Deutsches Krebsforschungszentrum, Heidelberg; ⁵ Department of Pediatric Oncology, University Children's Hospital, Cologne, Germany; and ⁶ Pediatric Oncology Branch, Oncogenomics Section, National Cancer Institute, Gaithersburg, Maryland

Requests for reprints: Kai-Oliver Henrich, Department of Tumour Genetics B030, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Phone: 49-6221-423220; Fax: 49-6221-423277; E-mail: k.henrich{at}dkfz.de.

Purpose: A distal portion of 1p is frequently deleted in human neuroblastomas, and it is generally assumed that this region harbors at least one gene relevant for neuroblastoma development. A 1p36.3 commonly deleted region, bordered by D1S2731 and D1S214 has been defined. The present study surveys whether expression of genes mapping to this region is associated with tumor behavior.

Experimental Design: Candidate genes localized within the deleted region were identified by sequence data analysis. Their expression was assessed in a cohort of 49 primary neuroblastomas using cDNA microarray analysis. Gene expression patterns associated with known prognostic markers and patient outcome were further evaluated by quantitative real-time reverse transcription-PCR in a cohort of 102 neuroblastomas.

Results: The commonly deleted region spans 261 kb and encompasses two genes, FLJ10737 and CAMTA1. We found no evidence for an association of FLJ10737 expression with established prognostic variables or outcome. In contrast, low CAMTA1 expression characterized tumors with 1p deletion, MYCN amplification, and advanced tumor stages 3 and 4. Moreover, low CAMTA1 expression was significantly associated with poor outcome (P < 0.001). In multivariate analysis of event-free survival, the prognostic information of low CAMTA1 expression was independent of 1p status, MYCN status, tumor stage, and age of the patient at diagnosis (hazard ratio, 3.52; 95% confidence interval, 1.21-10.28; P = 0.02).

Conclusions: Our data suggest that assessment of CAMTA1 expression may improve the prognostic models for neuroblastoma and that it will be important to define the biological function of CAMTA1 in this disease.

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