Cytogenetic analysis of uveal melanoma. Consistent occurrence of monosomy 3 and trisomy 8q

Abstract

Background: The genetic alterations associated with the pathogenesis of uveal melanoma have not been determined. To address this issue, the authors performed a prospective cytogenetic study of 35 uveal melanomas, including 23 primary untreated tumors and 12 tumors that were removed after local radiation therapy.

Methods: Representative tumor tissue was processed by established methods for histopathologic and cytogenetic studies. Tumor cells were disaggregated and established in short-term culture; metaphases were prepared by standard methods for karyotypic analysis.

Results: Successful analyses were achieved in 27 of the tumor specimens, including 20 of 23 tumors not exposed to radiation and 7 of 12 tumors exposed to radiation. All of the tumors had an abnormal karyotype. Recurrent chromosomal abnormalities detected in the tumors not exposed to radiation included monosomy 3 (13 of 20), trisomy 8 or 8q (11 of 20), loss of a sex chromosome (10 of 20), and loss of 6q (8 of 20). The tumors previously exposed to radiation were characterized by more complex changes, with monosomy 3 and trisomy 8q detected in three cases each.

Conclusions: Uveal melanoma is characterized by monosomy 3 and trisomy 8q in most cases. These findings, which are supported by data from other investigators, provide compelling evidence that loss of gene sequences on chromosome 3 and duplication of gene sequences on chromosome 8 are implicated in the genetic alterations associated with uveal melanoma and offer a basis for additional molecular genetic investigations.