Analysis of the retinoblastoma tumour suppressor gene in pancreatic endocrine tumours.
OBJECTIVE
The molecular pathogenesis of human pancreatic endocrine tumours (PETs) is largely unknown. One attractive candidate gene for involvement in pancreatic endocrine neoplasia is the retinoblastoma (Rb) tumour suppressor gene. A deletion of the Rb gene was recently described in a human insulinoma. In addition, mice harbouring a null mutation in the Rb gene bred with p53 mutant mice develop pancreatic endocrine tumours. Therefore, we sought to determine the role that allelic loss of Rb may play in a large series of human pancreatic endocrine tumours.


METHODS
46 pancreatic endocrine tumours were obtained from 41 patients. Utilizing genomic DNA isolated from the tumour samples and control normal cells, 2 highly polymorphic microsatellite loci (D13S153 and Rb 1.20) located within the Rb gene were PCR amplified and examined for loss of heterozygosity.


RESULTS
2 patients were homozygous at both loci and thus uninformative. The remaining 39 had informative markers at one or both of these loci, and none of the tumours from these patients demonstrated allelic loss of Rb.


CONCLUSIONS
In tumours in which Rb inactivation is pathogenetically important, somatic loss of one Rb allele commonly accompanies a point mutation or microdeletion within the other allele. Thus, the absence of demonstrable allelic loss in this large series strongly suggests that Rb gene inactivation is not frequently involved in the pathogenesis of human pancreatic endocrine tumours.
Chung
D C
DC
Laboratory of Endocrine Oncology, Massachusetts General Hospital, Boston 02114, USA.
Smith
A P
AP
Louis
D N
DN
Graeme-Cook
F
F
Warshaw
A L
AL
Arnold
A
A
D007516:Adenoma, Islet Cell / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D015408:Gastrinoma / Q000235:genetics; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D005819:Genetic Markers; D006801:Humans; D007340:Insulinoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*
D005819:Genetic Markers