Chromosome 22q in pancreatic endocrine tumors: identification of a homozygous deletion and potential prognostic associations of allelic deletions.

Objective: A variety of human tumors frequently show allelic deletions of chromosome 22q, suggesting that inactivation of one or more tumor suppressor genes in this region is important for their tumorigenesis.

Methods: In this study, 23 patients with pancreatic endocrine tumors (PETs), including gastrinomas, VIPomas and non-functioning islet cell carcinomas, were analyzed for loss of heterozygosity (LOH) on chromosome 22q with 12 microsatellite and 7 sequence tagged site markers.

Results: LOH on chromosome 22q was identified in 22 of 23 (96%) PETs. Markers in the chromosomal region 22q12.1 revealed LOH rates up to 85%. Notably, one tumor revealed a homozygous deletion in a second region at 22q12.3. LOH at this locus occurred more frequently in tumors with distant metastases (10 of 11) compared with tumors without distant metastases (3 of 12; P=0.0057) and, overall, allelic loss of 22q is positively correlated with distant metastases (r=0.78; P<0.0001).

Conclusions: These findings are suggestive for novel tumor suppressor gene loci at chromosome 22q that might contribute to the pathogenesis of PETs, especially to the development of distant metastases.