[Frequent loss of heterozygosity at MEN-1 gene and chromosome 22q in insulinomas and its significance].

OBJECTIVE

To detecte whether loss of heterozygosity (LOH) at the MEN-1 locus as well as 22q occurs in sporadic insulinoma and if LOH can be used as a genetic marker to differentiate malignant and benign insulinomas.

METHODS

MEN-1 gene and 22q allelotyping were performed by PCR with microsatallite markers in DNA from microdissected normal and tumor tissues from archived or frozen insulinomas (8 malignant and 32 benign, from 38 patients). The significance was calculated using t test and Cochran-Mantel-Haenszel Statistics, P < 0.05 was considered significant.

RESULTS

Sixteen of the 40 insulinomas (40.0%) had MEN-1 LOH and 22q LOH was shown in 30 of the 40 tumors (75.0%). Eleven of the 30 tumors (37.0%) with 22q LOH had 22q12 LOH over a 3 cm region, whereas LOH in 14 tumors (47.0%) occurred at 22q13.3. Eight tumors with D22S 280 locus (22q12) LOH were shown without MEN-1 LOH while 14 of the 30 tumors without D22S280 LOH had MEN-1 LOH (0% vs 47%, P = 0.016). Six of the 14 tumors (43.0%) with 22q13.3 LOH were malignant, whereas 2 of 26 tumors without 22q13.3 LOH (8.0%) are malignant (P = 0.0088).

CONCLUSION

MEN-1 gene LOH may contribute to a proportion of insulinomas, and 22q LOH occurs frequently in insulinomas. D22S 280 (22q12) LOH may independently contribute to the tumorogenesis of sporadic insulinoams, whereas detecting 22q13.3 LOH in insulinomas can be a potential genetic marker to distinguish malignancy from benign tumors.