Loss of chromosome 3 alleles and multiplication of chromosome 8 alleles in uveal melanoma

Abstract

Uveal melanoma is the most frequent primary intraocular tumor. The etiology is unknown. Using neutral DNA polymorphisms on chromosomes 2, 3, and 8, we have detected loss of chromosome 3 alleles in 8 of 13 tumors and multiplication of chromosome 8 alleles in 6 of 11 tumors. No anomalies at a locus on chromosome 2 were found in 10 of 10 tumors. These results confirm and extend previous cytogenetic findings and suggest that a tumor suppressor gene on chromosome 3 and an oncogene on chromosome 8 may be involved in the formation or progression of this tumor.

Cytogenetic analysis of posterior uveal melanoma

“…As recognized in earlier studies, chromosomes 3, 6, and 8 are frequently altered in this malignancy [5][6][7][8][9][10]. Loss of an entire chromosome 3 was the sole visible cytogenetic aberration observed in case M91-003 (Table 2).…”

“…These studies have implicated monosomy 3, i(8)(ql0), trisomy 8, and alterations in 6 as primary chromosomal alterations in the development of this tumor [5][6][7][8][9]. Recently, restriction fragment length polymorphism analysis has confirmed the cytogenetic results indicating loss of heterozygosity on chromosome 3 and overrepresentation of 8q [10]. Loss of alleles on chromosome 2 has also been reported [11], but there have been no reported cytogenetic alterations involving this chromosome.…”

Chromosome 3 Status in Uveal Melanoma: A Comparison of Fluorescence In Situ Hybridization and Single-Nucleotide Polymorphism Array

“…1,2 These aberrations were later shown to correlate with poor prognosis. [3][4][5] Of various cytogenetic abnormalities observed, monosomy 3 is the strongest predictor of metastatic risk. [5][6][7][8][9][10][11][12][13][14] Several techniques are currently being used to detect monosomy 3 and other chromosomal changes associated with the development of metastatic disease.…”

Things that go bump in the light. The differential diagnosis of posterior uveal melanomas

“…Indeed, studies in our own laboratory and those of others have identified specific chromosome alterations in uveal melanomas. [20][21][22][23] Moreover, it would appear that some of these changes (notably alterations of 3 and 8) correlate strongly with prognosis, [24][25][26] suggesting that these particular changes are relatively late changes in the progression to a metastatic phenotype. Thus if one accepts that uveal melanomas arise as a result of a sequence of several genetic mutations, then it is possible to speculate that some early genetic mutations may have occurred in IMLs; but that the process has arrested before a complete malignant phenotype has developed.…”