Allelic variants of CAMTA1 and FLJ10737 within a commonly deleted region at 1p36 in neuroblastoma Kai-Oliver Henrich a, *, Andreas Claas a,d , Christian Praml a , Axel Benner b , Jan Mollenhauer c Annemarie Poustka c , Manfred Schwab a , Frank Westermann a a Division of Tumour Genetics B030, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany b Central Unit Biostatistics, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany c Division of Molecular Genome Analysis B050, German Cancer Research Center DKFZ, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany ARTICLE INFO Article history: Received 23 June 2006 Received in revised form 12 September 2006 Accepted 19 September 2006 Keywords: CAMTA1 FLJ10737 1p Neuroblastoma Deletion LOH ABSTRACT Deletion of a distal portion of 1p is seen in a wide range of human malignancies, including neuroblastoma. Here, a 1p36.3 commonly deleted region of 216 kb has been defined encom- passing two genes, CAMTA1 and FLJ10737. Low expression of CAMTA1 has been recently shown to be an independent predictor of poor outcome in neuroblastoma patients. The present study surveys CAMTA1 and FLJ10737 for genetic alterations by fluorescence-based single strand conformation polymorphism (SSCP) using a panel of DNAs from 88 neurobl- astomas, their matching blood samples and 97 unaffected individuals. Nucleotide variants encoding amino acid substitutions were found in both genes. One CAMTA1 variant (T1336I) was not detected in 97 unaffected individuals, another (N1177K) resides in a conserved domain of the CAMTA1 protein and was found hemizygous in six neuroblastomas. We found no evidence for somatic mutations in FLJ10737 or CAMTA1. Further investigations are needed to address the functional impact of the identified variants and their possible significance for neuroblastoma. Ó 2006 Elsevier Ltd. All rights reserved. 1. Introduction Neuroblastoma is an embryonal tumour consisting of neural crest derived undifferentiated neuroectodermal cells that accounts for 9% of all childhood cancers. The clinical hall- mark of this tumour is its extreme heterogeneity, ranging from spontaneous regression to malignant progression. An aggressive subtype of neuroblastomas is characterised by genetic aberrations including amplification of the MYCN oncogene 1,2 and deletion of a distal portion of 1p. The inci- dence of 1p deletion in neuroblastoma is 30% and it has been shown that 1p36 loss of heterozygosity (LOH) is an independent predictor of disease progression. 3,4 Functional evidence supporting a role of 1p in neuroblastoma derives from experiments in which the introduction of 1p chromo- somal material into neuroblastoma cells resulted in reduced tumourigenicity. 5 Thus, it is generally believed that 1p con- tains a gene (or genes) important in the development of neuroblastoma. For almost two decades numerous studies have at- tempted to narrow down the 1p deleted region in order to increase the chances for identifying the gene(s) of inter- est. 6–14 However, so far, the success in defining candidate genes is limited as most of the identified regions were too large to pinpoint single genes. Recent studies made it possi- ble to considerably narrow down a smallest region of consis- 0959-8049/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2006.09.023 * Corresponding author: Tel.: +49 6221 423220; fax: +49 6221 423277. E-mail address: k.henrich@dkfz.de (K.-O. Henrich). d Present address: Population Genetics Technologies Ltd., Babraham Research Campus, Babraham, Cambridgeshire CB2 4AT, UK. EUROPEAN JOURNAL OF CANCER 43 (2007) 607 – 616 available at www.sciencedirect.com journal homepage: www.ejconline.com