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S. Itty, J. G. Keefe, J. S. Pulido, E. C. Thorland, D. L. Knutson, D. R. Salomao; A Dual Probe FISH Strategy Effectively Detects Monosomy 3 in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3379.
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The presence of chromosome 3 monosomy in uveal melanoma is an important predictor of poor survival. Current FISH methods using a single chromosome 3 centromeric probe may not optimally detect monosomy because of inherent variability in tumor characteristics and sectioning. A dual-probe FISH strategy was developed using probes targeted to the centromere (colored red) and q arm (green) of chromosome 3 to establish a better cutoff for the determination of monosomy 3.
The dual-probe FISH strategy was validated by comparing red (R) and green (G) signals together in 17 melanoma and 20 non-melanoma samples. The cut-off was calculated using the binomial expansion formula and the number of false-positive cells for the normal samples. The clinical records of the 17 melanoma patients were then assessed for evidence of metastatic disease.
The normal cutoff for monosomy 3 was calculated to be greater than 23% nuclei with a 1R1G signal pattern; of 17 melanoma samples, 11 were determined to have monosomy 3 using this cutoff. Initial clinical data demonstrated metastasis in 6 of the 17 melanoma samples; of these six, five were monosomy by FISH. Of 11 without metastasis, six had monosomy 3, though follow-up was limited to less than 26 months in these samples and thus may still be at high risk to develop metastasis at longer follow-up intervals. Only one patient without monosomy 3 was found to have metastatic disease. A different genetic mechanism for inactivating genes on chromosome 3 may have occurred in the tumor in this patient.
The dual probe FISH method is an effective method for establishing the presence of monosomy 3 in uveal melanoma and will be useful in clinical management of these patients.
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