DPC4 SPLICE VARIANTS IN NEUROBLASTOMA

One of the loci for neuroblastoma suppressor genes is chromosome 18q21 where the DPC4 tumor suppressor gene, as well as the DCC and MADR2 ge nes, is located. DPC4 is a molecule of the TGF-P signal which regulate s differentiation of the neural crest precursor cells from which neuro blastoma originates. During the search for the significance of DPC4 as a candidate neuroblastoma suppressor gene, we found that there are at least two variant forms of the DPC4 transcripts by using the reverse- transcriptase-PCR procedure. The subsequent sequencing analysis has re vealed that one is missing exons 5 and 6 and the other is missing exon s 4-6. Both splice variants were frequently observed in neuroblastomas and at low levels in normal tissues. Though the functional role of th e DPC4 splice variants is unknown, they might be important in regulati ng the TGF-P signaling not only in neuroblastomas but also in other tu mors and normal tissues. (C) 1998 Elsevier Science Ireland Ltd.