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The structure of the GH gene in human somatotrophinomas was examined in terms of promoter region sequence and degree of methylation. In six tumours, the promoter sequence did not differ from that observed in the corresponding genomic (white blood cell-derived) DNA, suggesting that it is unlikely that excessive GH production is due to a point mutation within this region. In contrast, Southern blot analysis using the methylation-sensitive restriction enzymes HpaII and HhaI revealed lower levels of methylation of the GH gene in somatotrophinomas when compared with that found in DNA derived from normal pituitary glands. We conclude that hypomethylation of the GH gene in human somatotrophinomas may play at least a partial role in excessive GH production.

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