Microsatellite analysis of 9p2i in primary uveal melanoma

Purpose. Uveal melanoma is the most common primary intraocular malignancy in adults and the second most common site of origin of malignant melanoma. Local tumor control, frequently accomplished by enucleation, iocal resection, and radiation therapy, ean result in significant visual morbidity. At least 30% of affected patients develop metastatic melanoma within 10 years of successful local management of the primary neoplasm, and the mean survival time for patients with liver metastases is 7 months. Although current methods can provide some prognostic information, elucidation of the molecular genetic events that underlie (he transformation of a uveal melanocyte into a melanoma is needed. Methods. DNA from 28 primary choroidai or ciliochoroidal tumors and the matched normal eye structures was extracted form paraffin-embedded tissue. Normal and tumor DNA was amplified by polymerase chain reaction (PCR) using microsalellite markers which allows identification of areas of chromosomal loss that may conlain critical suppressor genes important in the development of melanoma. Fourteen highly informative microsatellite markers around the p!6 locus, a candidate (umor suppressor gene on 9p21 shown to be important in sporadic and familial cutaneous melanoma, were used to determine the frequency of loss of heterozygosity (LOH). Results. LOH of one or more of the markers tested on 9p21 was observed in 11 of 28 uveal melanomas studied. The majority of hemizygous losses mapped near p16. The contribuiion of inactivation by homozygous deletion in this region is currently being determined. Genetic alterations of the p16 gene, as well as other candidate loci, are also being examined . Conclusions. LOH in the region oi' p 16 on 9p21 suggests that this tumor suppressor gene, or other genes in this region, may play a role in the development of uveal melanoma. Further studies to determine the earliest genetic changes that occur during the natural history of tumor progression from a localized precursor lesion lo a primary neoplasm to metastatic disease may lead to novel diagnostic approaches, identification of prognostic indicators, and novel therapeutic advances based on these changes.