Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours.

• The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT-PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.

Nyckelord

Alleles

Amino Acid Sequence

Apoptosis

genetics

Base Sequence

Case-Control Studies

Caspase 9

Caspases

genetics

metabolism

Chromosomes

Human

Pair 1

genetics

Cloning

Molecular

DNA Mutational Analysis

DNA Primers

chemistry

DNA

Neoplasm

analysis

Gene Frequency

Genes

Tumor Suppressor

Humans

Molecular Sequence Data

Mutation

Neoplasm Proteins

genetics

metabolism

Neuroblastoma

genetics

metabolism

Polymerase Chain Reaction

Proteins

genetics

metabolism

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)