Genome-wide allelotypes of familial pancreatic XXXX and familial and @entity70768 .

@entity1 @entity70768 @entity788 @entity4929 @entity5 @entity420
PURPOSE: Most @entity5 susceptibility genes are @entity5 suppressor genes that are biallelically inactivated in familial @entity5 through somatic deletion of the wild-type allele. Identifying the genomic losses that occur in @entity788 , particularly those that occur in @entity5 , may help localize the genes responsible for @entity788 susceptibility. EXPERIMENTAL DESIGN: Normal and neoplastic tissue DNA was isolated from fresh-frozen surgically resected tissues from 20 @entity1 with primary @entity788 (defined as having at least one first-degree relative with @entity788 ), 31 with @entity70768 ( @entity4929 ), and 7 with familial IPMNs using laser capture microdissection. Microdissected DNA was whole genome amplified using multiple strand displacement. Genome-wide allelotypes were determined using 391 microsatellite markers. The accuracy of microdissection and fidelity of the whole genome amplification were determined by comparing the genotypes of microdissected primary @entity788 to the genotypes of xenografts derived from these @entity5 and by comparing the results of amplified to nonamplified specimens. RESULTS: The concordance of genotypes between LCM whole genome amplified primary @entity788 and their corresponding @entity788 xenograft DNAs was 98%. Among the 20 primary familial pancreatic @entity420 , we found a high prevalence of loss of heterozygosity (LOH) with an average fractional allelic loss (FAL) of 49.9% of an aggregate of 2,378 informative markers. The level of FAL in the IPMNs (10%) was significantly lower than in the pancreatic @entity420 . The most common locus of LOH in the IPMNs was at 19p (LOH at 24% of markers). The regions of frequent allelic loss observed in the @entity788 were similar to those found in sporadic @entity788 . CONCLUSIONS: The allelic loss patterns of @entity5 and IPMNs provide clues as to the genomic locations of @entity5 suppressor genes inactivated in these @entity5 .
