Pancreatic endocrine tumours: evidence for a tumour suppressor pathogenesis and for a tumour suppressor gene on chromosome 17p.
Two molecular pathways leading to cancer are known. Common-type cancers arise from the 'tumour suppressor' pathway, characterized by gross chromosomal changes and allelic losses (LOH) in an average of 25 per cent or more of randomly chosen chromosomal loci. The 'mutator pathway' has been recognized in a subset of cancers, characterized by widespread microsatellite DNA instability and rarity of chromosomal losses. The present study has investigated 20 pancreatic endocrine tumours (PETs) for loss of heterozygosity (LOH) at seven chromosomal loci (3p14, 7q31-32, 11q13, 13q14, 18q21, 17p13, and 17q21); microsatellite instability; and Ki-ras, N-ras, and p53 gene mutations. LOH was found in an average of 24 per cent of the chromosomal loci analysed. No tumour showed microsatellite instability. Ki-ras and p53 mutations were each found in one case. The frequency of losses was higher in malignant (40 per cent) than in benign (17 per cent) tumours (p = 0.009), and the specific chromosome 17p13 LOH was associated with extrapancreatic extension of disease (p = 0.007), high proliferative activity (p = 0.001), and absence of progesterone receptors (p = 0.01). A common deleted region on chromosome 17p13 and the rarity of p53 gene mutations suggest the existence of a novel tumour suppressor gene involved in the pathogenesis of PETs in this chromosomal area.
Beghelli
S
S
Istituto di Anatomia Patologica Università di Verona, Italy.
Pelosi
G
G
Zamboni
G
G
Falconi
M
M
Iacono
C
C
Bordi
C
C
Scarpa
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D002886:Chromosomes, Human, Pair 17; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000378:metabolism
D019394:Ki-67 Antigen; D011980:Receptors, Progesterone