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.
Wild
Anja
A
Department of General Surgery, Philipps-University of Marburg, Baldingerstrasse, Marburg/Lahn 35043, Germany.
Langer
Peter
P
Celik
Ilhan
I
Chaloupka
Brunhilde
B
Bartsch
Detlef K
DK
D000328:Adult; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D015408:Gastrinoma / Q000235:genetics*; D017353:Gene Deletion; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007515:Islets of Langerhans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011379:Prognosis
D005819:Genetic Markers