Henriquez Fiona, Janssen Christoph, Kemp Ewan G, Roberts Fiona
School of Engineering and Science, University of Paisley, Paisley, Scotland, UK.
Invest Ophthalmol Vis Sci. 2007 Nov;48(11):4897-900. doi: 10.1167/iovs.07-0440.
An activating mutation in exon 15 of the BRAF gene has been found in a high proportion of cutaneous pigmented lesions, but only in one case of uveal melanoma. Iris melanoma is the least common uveal melanoma and displays a less aggressive clinical course compared with posterior uveal melanoma. To date, no study has been conducted to investigate the T1799A mutation in iris melanoma. The purpose of this study was to determine whether the T1799A BRAF mutation is present in iris melanoma.
DNA was extracted from 19 archival, paraffin-embedded tissue sections of iris melanomas. Nested PCR was used to amplify exon 15 of the BRAF gene, and the product was purified, cloned into a sequencing vector, and sequenced. The sequences obtained were compared with the wild-type sequence of the BRAF gene. The presence or absence of the BRAF mutation was also compared with the clinicopathological features.
The T1799A mutation was identified by sequencing in 9 of 19 iris melanomas. Six of the 9 cases with the BRAF mutation were recurrent tumors. All other tumors were resections for primary tumors. There was a statistically significant association between the BRAF mutation and recurrent tumor (P = 0.003). There was no association between the presence of the BRAF mutation and other clinicopathological characteristics.
In this small study, the T1799A BRAF mutation was identified in almost half of the iris melanoma tissues samples examined. This finding suggests that there may be genetic as well as clinical differences between iris and posterior uveal melanomas.
在高比例的皮肤色素沉着病变中发现了BRAF基因第15外显子的激活突变,但仅在1例葡萄膜黑色素瘤中发现。虹膜黑色素瘤是最罕见的葡萄膜黑色素瘤,与后葡萄膜黑色素瘤相比,其临床病程侵袭性较小。迄今为止,尚未有研究调查虹膜黑色素瘤中的T1799A突变。本研究的目的是确定虹膜黑色素瘤中是否存在T1799A BRAF突变。
从19例存档的虹膜黑色素瘤石蜡包埋组织切片中提取DNA。采用巢式PCR扩增BRAF基因第15外显子,产物经纯化后克隆到测序载体中并进行测序。将获得的序列与BRAF基因的野生型序列进行比较。还将BRAF突变的有无与临床病理特征进行比较。
通过测序在19例虹膜黑色素瘤中的9例中鉴定出T1799A突变。9例有BRAF突变的病例中有6例为复发性肿瘤。所有其他肿瘤均为原发性肿瘤切除术。BRAF突变与复发性肿瘤之间存在统计学显著关联(P = 0.003)。BRAF突变的存在与其他临床病理特征之间无关联。
在这项小型研究中,在所检测的几乎一半虹膜黑色素瘤组织样本中鉴定出了T1799A BRAF突变。这一发现表明虹膜和后葡萄膜黑色素瘤之间可能存在基因以及临床差异。