New splicing variants for human Tyrosine Hydroxylase gene with possible implications for the detection of minimal residual disease in patients with neuroblastoma

Expression of Tyrosine Hydroxylase (TH) is frequently seen in neuroblastomas, the most common extracranial tumor in children, and TH mRNA detection is used for the analysis of microcirculating or micrometastatic disease in this neoplasia. TH is known to have at least seven isoforms produced by alternative splicing of the N-terminal region (exons 1-4), although no other splicing variants have been described downstream. TH expression was analyzed in six samples of neuroblastoma by RT-PCR using highly restrictive conditions and primers between exons 5 and 12, a region of the gene previously considered to be constant. In the analyzed samples we found two novel TH mRNAs, one lacking exon 8, and another lacking exons 8+9. These new splicing variants are described in a region of TH previously reported to be conserved, and that has been used for the design of reverse transcriptase-polymerase chain-reaction assays for the detection of minimal residual disease [Eur. J. Cancer, 27 (1991) 762]. The splicing pattern characteristic of every tumor could allow the monitoring of the minimal residual disease in a tumor-specific manner.