CHROMOSOME 9P DELETIONS IN INVASIVE AND NONINVASIVE NONFUNCTIONAL PITUITARY-ADENOMAS - THE DELETED REGION INVOLVES MARKERS OUTSIDE OF THE MTS1 AND MTS2 GENES

We have screened 57 cases of primary, nonfunctional, pituitary adenoma s for loss of heterozygosity of markers on chromosome 9p. Using a pane l of 11 microsatellite markers, we found hemizygous deletion with at l east one of the markers in 18 tumors (31.5%). The frequency of loss wa s similar in both noninvasive (8 of 26; 31%) and invasive tumors (10 o f 31; 32%), suggesting that loss on this chromosome might he an early event in pituitary tumorigenesis. Two discrete areas of loss were punc tuated by a region of retention of heterozygosity between the markers D9S171 and IFNA, indicative of homozygous deletion. However, multiplex PCR analysis (MTS1 and MTS2) and the presence of a 31 untranslated re gion polymorphism in MTS1 suggested that neither of these tumor suppre ssor genes was homozygously deleted. In 6 of the 18 tumors showing LOH , sufficient DNA was also available for Southern blot analysis and, in all cases, showed retention of MTS1. Cell mixing experiments of tumor cell DNA homozygously deleted for MTS1 with DNA in which neither copy of the gene was deleted only gave rise to a signal at contamination l evels greater than 30% and could discriminate homozygous and hemizygou s loss. These studies support the recent findings that mechanisms othe r than hemi- and homozygous deletion are most likely responsible for t he loss of MTS1 gene product in pituitary tumors (M. Woloschak et al., Cancer Res., 56: 2493-2486, 1996.). These data show that losses on ei ther side of 9p21-22, both or either of which may be deleted, are invo lved in pituitary tumorigenesis and provide evidence for distinct supp ressor gene loci, in addition to MTS1, on chromosome 9p.