IDENTIFICATION OF BRAIN-SPECIFIC SPLICING VARIANTS OF THE HDLG1 GENE AND ALTERED SPLICING IN NEUROBLASTOMA CELL-LINES

The human homologue of Drosophila tumor suppressor dig, hDLG1, is one of the proteins known to interact with APC, a tumor suppressor for col orectal cancer. Alternative splicing of this gene generates transcript s either with [insertion 1 (II)] or without 99 nucleotides in the 5' p art of the dig homology repeats (DHR) domain. We found almost equivale nt expression of these two splicing variants in most human tissues; ho wever, in skeletal muscle the transcript with the 99-bp insertion was predominant, and in the brain, that without the 99-bp insertion was ex pressed predominantly. We also examined alternative splicing in the re gion between the SH3 and GUK domains where two different sizes of inse rtions, 34 nucleotides (I2) or 100 nucleotides (I3), had been reported , and found various splicing patterns among the tissues examined. In b rain we detected six different, alternatively spliced transcripts, two of which included a novel, 36-bp, brain-specific exon encoding a pept ide bearing significant homology to a portion of rat synapse-associate d protein, SAP97/PSD95. Subsequently, we investigated the splicing pat terns of the hDLG1 gene in 24 neuroblastoma cell lines. In two-thirds of these lines, the splicing patterns were altered from those observed in normal brain tissue. As one-third retained the normal brain-splici ng pattern, the loss of normal splicing of hDLG1 may not in itself cau se formation of tumors, but it might reflect the biological character of individual neuroblastomas.