Chromosome 13q deletion mapping in pituitary tumors: Infrequent loss of the retinoblastoma susceptibility gene (RB1) locus despite loss of RB1 protein product in somatotrophinomas

Two recent studies have described allelic loss of an RB1 intragenic marker on chromosome 13q in aggressive and metastatic pituitary tumors that did no t correlate with loss of pRB, The second report also showed that losses a e re more frequently associated with a more centromeric marker. Because both of these studies suggest the presence of another or other tumor suppressor genes (TSGs) on 13q, we carried out an allelotype analysis encompassing kno wn and recently described TSG loci on 13q, together with immunohistochemica l analysis of pRB. We analyzed 82 nonfunctional tumors and 53 somatotrophinomas subdivided int o invasive and noninvasive cohorts. A significantly higher frequency of los s, at one or more of 13 markers, was evident in the invasive nonfunctional tumors (54%, 26 of 38) than in their noninvasive counterparts (29%, 10 of 3 4). An approximately equal frequency of loss was apparent in invasive (28%, 5 of 18) and noninvasive (31%, 11 of 35) somatotrophinomas at one or more markers. In those tumors harboring deletion, loss at two or more markers wa s more frequent in invasive nonfunctional tumors 65% (17 of 26) compared wi th 36% (4 of 11) of their noninvasive counterparts. In somatotrophinomas, 4 0% (2 of 5) of invasive tumors as compared with 64% (7 of 11) of noninvasiv e tumors had evidence of two or more deletions. In tumors showing loss at t wo or more loci, the majority showed large deletions; however, loss of the RBI intragenic marker D13S153 was infrequent. In most cases, loss at indivi dual markers was more frequent in invasive tumors than their noninvasive co unterparts. A marker 3 CM telomeric to RB1 (D13S1319) showed the highest fr equency of deletion in both invasive cohorts (29% of somatotrophinomas and 24% of nonfunctional tumors). Immunohistochemical analysis of pRB showed frequent loss in somatotrophinom as (27%, 9 of 33) in comparison with 4% (2 of 53) of nonfunctional tumors. Although loss of pRB did not correlate with loss of an intragenic marker or tumor grade, it was significantly associated with the somatotrophinoma sub type (P = 0.002). These data suggest that chromosome 13q is a frequent targ et for allelic deletion in pituitary tumors and point to another or other T SG loci in these regions.