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BRAF Mutations in Conjunctival Melanoma

¹From the Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, Scotland, United Kingdom; and the ²Contributed equally to the work and therefore should be considered equivalent senior authors. ³University Department of Pathology Western Infirmary, Glasgow, Scotland, United Kingdom.

PURPOSE. An activating mutation in exon 15 of the BRAF gene has been found in a high proportion of cutaneous melanomas and cutaneous nevi but not in uveal melanoma. Conjunctival melanoma shows greater clinical similarity to cutaneous melanoma than does uveal melanoma. The purpose of this study was to determine whether the T1799A BRAF mutation found in cutaneous melanoma is also present in conjunctival melanoma.

METHODS. DNA was extracted from paraffin sections obtained from glutaraldehyde or formalin-fixed, paraffin-embedded conjunctival melanomas. Forty-two specimens were identified from 25 patients. Seminested PCR was used to amplify exon 15 of the BRAF gene, and the resultant PCR product was purified and directly sequenced. Sequences from conjunctival melanomas were compared with the wild-type sequence of the BRAF gene. The presence or absence of the BRAF mutation was compared with the clinicopathological features.

RESULTS. The T1799A (V600E) mutation was detected by sequencing in melanomas from 5 of 22 patients as well as in the positive control, a cutaneous melanoma cell line. In this small series, no statistically significant associations between the presence of the BRAF mutation and clinicopathological characteristics were detected, although tumors with this mutation tended to have a larger diameter and greater depth of invasion and to contain epithelioid cells.

CONCLUSIONS. Others have demonstrated a BRAF T1799A-activating mutation in cutaneous but not uveal melanoma. In this study, this BRAF mutation was demonstrated in some conjunctival melanoma tissue samples, suggesting that some conjunctival melanomas may share biological features in common with cutaneous melanoma.

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