Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients.
OBJECTIVE
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.


METHODS
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.
Henrich
Kai-Oliver
KO
Department of Tumour Genetics B030, Molecular Genetics B060, Deutsches Krebsforschungszentrum, Heidelberg, Germany. k.henrich@dkfz.de
Fischer
Matthias
M
Mertens
Daniel
D
Benner
Axel
A
Wiedemeyer
Ruprecht
R
Brors
Benedikt
B
Oberthuer
André
A
Berthold
Frank
F
Wei
Jun Stephen
JS
Khan
Javed
J
Schwab
Manfred
M
Westermann
Frank
F
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; C487554:CAMTA1 protein, human; D002135:Calcium-Binding Proteins; D015534:Trans-Activators