Molecular characterization of pancreatic serous microcystic adenomas - Evidence for a tumor suppressor gene on chromosome 10q

Pancreatic serous microcystic adenomas (SCAs) are rare, benign tumors with a striking female preference. Virtually no information is available about c hromosomal or genetic anomalies in this disease. We performed extensive mol ecular characterization of 21 cases of formalin-fixed, paraffin-embedded sp oradic SCAs consisting in genome-wide allelic loss analysis with 79 microsa tellite markers covering all 22 autosomes, assessment of microsatellite ins tability, and mutational analysis of the VHL, K-ras, and p53 genes in nine cases for which frozen tissue was available. Although no case showed micros atellite instability of the type seen in mismatch repair-deficient tumors, a relatively low fractional allelic loss of 0.08 was found. Losses on chrom osome 10q were the most frequent event in SCAs (50% of cases), followed by allelic losses on chromosome 3p (40% of cases). Moderately frequent losses (>25% of cases) were found on chromosomes 1q, 2q, and 7q. The VHL gene, loc ated on chromosome 3p, had somatic inactivating mutations in two of nine ca ses (22%), whereas no mutations were found in either K-ms or p53, in agreem ent with the finding that all 21 cases stained negative for p53 by immunohi stochemistry. Our study indicates that the involvement of chromosomal. arms 10q and 3p is characteristic of SCAs and that the VHL gene is involved in a subset of sporadic cases.