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<p>Abstract</p> <p>Background</p> <p><it>CYYR1 </it>is a recently identified gene located on human chromosome 21 whose product has no similarity to any known protein and is of unknown function. Analysis of expressed sequence tags (ESTs) have revealed high human <it>CYYR1 </it>expression in cells belonging to the diffuse neuroendocrine system (DNES). These cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was to conduct an initial analysis of sequence, splicing and expression of the <it>CYYR1 </it>mRNA in human NE tumors.</p> <p>Methods</p> <p>The <it>CYYR1 </it>mRNA coding sequence (CDS) was studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative splicing was identified generating two isoforms of <it>CYYR1 </it>mRNA differing in terms of the absence (CAG^-isoform, the first described mRNA for <it>CYYR1 </it>locus) or the presence (CAG⁺isoform) of a CAG codon. When present, this specific codon determines the presence of an alanine residue, at the exon 3/exon 4 junction of the <it>CYYR1 </it>mRNA. The two mRNA isoform amounts were determined by quantitative relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal tissues. A bioinformatic analysis was performed to search for the existence of the two <it>CYYR1 </it>isoforms in other species.</p> <p>Results</p> <p>The <it>CYYR1 </it>CDS did not show differences compared to the reference sequence in any of the samples, with the exception of an NE tumor arising in the neck region. Sequence analysis of this tumor identified a change in the CDS 333 position (T instead of C), leading to the amino acid mutation P111S. NE tumor samples showed no significant difference in either <it>CYYR1 </it>CAG^-or CAG⁺isoform expression compared to control tissues. <it>CYYR1 </it>CAG^-isoform was significantly more expressed than CAG⁺isoform in NE tumors as well as in control samples investigated. Bioinformatic analysis revealed that only the genomic sequence of <it>Pan troglodytes CYYR1 </it>is consistent with the possible existence of the two described mRNA isoforms.</p> <p>Conclusion</p> <p>A new "subtle" splicing isoform (CAG⁺) of <it>CYYR1 </it>mRNA, the sequence and the expression of this gene were defined in a large series of NE tumors.</p>