Through the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative @entity5 -suppressor gene (TSG) loci in sporadic @entity977 . This study reports a genome-wide allelotyping by use of 122 microsatellite markers in a large cohort of @entity5 , consisting of @entity10759 and non-functioning @entity652 . Samples were first subject to prior whole genome amplification by primer extension pre-amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole-genome analysis with this number of microsatellite markers. The overall mean frequency of @entity3 was significantly higher than that in their non-invasive counterparts (7 vs. 3% @entity10759 ; 6 vs. 3% non-functioning @entity652 , respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in @entity10759 and 10 in @entity5 , with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive @entity5 than in their non-invasive counterparts, suggesting these to be markers of @entity5 progression. Other regions showed similar frequencies of LOH in both invasive and non-invasive @entity5 , implying these to be early changes in pituitary tumorigenesis. This genome-wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype-specific and were found at a higher frequency in invasive @entity5 than in their non-invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype-specific. This investigation provides an unbiased estimate of global aberrations in sporadic @entity977 as assessed by LOH analysis. The identification of multiple "hotspots" throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic-mediated gene-silencing events.

Genome-wide amplification and allelotyping of sporadic XXXX identify novel regions of genetic loss.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'non-functioning tumors', 'tumors'] @entity977 :: ('MESH:D010911', 'Disease') :: ['pituitary tumors'] @entity3 :: ('MESH:D009362', 'Disease') :: ['loss in invasive tumors'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas'] @entity10759 :: ('MESH:D049912', 'Disease') :: ['somatotrophinomas']
@entity977 :: (MESH:D010911,Disease) :: ['pituitary adenomas']
