Multiplex Ligation-Dependent Probe Amplification of Conjunctival Melanoma Reveals Common BRAF V600E Gene Mutation and Gene Copy Number Changes
Multiplex Ligation-Dependent Probe Amplification of Conjunctival Melanoma Reveals Common BRAF V600E Gene Mutation and Gene Copy Number Changes
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DOI：
10.1167/iovs.10-6934
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Damato, Bertil E.
中科院分区：
文献类型：
--
作者：
Lake, Sarah L.;Jmor, Fidan;Damato, Bertil E.
目的。确定原发性和转移性结膜黑色素瘤（CoMs）中BRAF V600E基因突变的发生和所有常染色体臂和已知在肿瘤发生中经常改变的基因的拷贝数变化。DNA （200 ng）通过三种多重连接依赖探针扩增法（P027葡萄膜黑色素瘤、P036人端粒和P206海绵样黑色素瘤）进行分析。16例原发肿瘤样本中有8例，6例转移性肿瘤样本中有4例出现BRAF V600E基因突变。CDKN1A和RUNX2（均为6p21.2）分别在21例原发性CoMs中的11例和16例中扩增。在转移性CoMs中，MLH1 （3p22.1）和TIMP2 （17q25.3）频繁扩增，MGMT （20q26.3）和ECHS1 （10q26.3）频繁缺失。BDH （3q）、FLJ20265 （4p）、OPRL1 （20q）和PAO （10q）基因在P036检测中代表各自染色体臂的端粒，在转移性CoMs中经常扩增。BRAF突变或CDKN1A或RUNX2扩增与性别、年龄、组织学细胞类型或患者生存率之间没有统计学意义的关联。没有拷贝数变化与转移性CoMs完全相关。然而，CDKN1A和RUNX2在CoMs发展中的作用以及MLH1、TIMP2、MGMT和ECHS1在转移性CoMs中的作用有待进一步研究。在更大的原发性和转移性CoMs队列中，有必要对观察到的基因和染色体臂拷贝数变化进行验证，以确定CoMs转移风险最高的患者。（Invest Ophthalmol Vis Sci. 2011;52:55 598-5604） DOI:10.1167/iovs.10-6934
PURPOSE. To determine the occurrence of BRAF V600E gene mutations and copy number changes of all autosome arms and genes known to be frequently altered in tumorigenesis in primary and metastatic conjunctival melanomas (CoMs).METHODS. DNA (200 ng) was analyzed by three multiplex ligation-dependent probe amplification assays (P027 uveal melanoma, P036 human telomere, and P206 spitzoid melanoma).RESULTS. Eight of 16 primary tumor samples and 4 of 6 metastatic samples showed BRAF V600E gene mutations. CDKN1A and RUNX2 (both 6p21.2) were amplified in 11 and 16 of 21 primary CoMs, respectively. In metastatic CoMs, MLH1 (3p22.1) and TIMP2 (17q25.3) were frequently amplified, and MGMT (20q26.3) and ECHS1 (10q26.3) were frequently deleted. The BDH (3q), FLJ20265 (4p), OPRL1 (20q), and PAO (10q) genes, representing the telomeres of their respective chromosome arms in the P036 assay, were frequently amplified in metastatic CoMs. No statistically significant associations were identified between BRAF mutation or CDKN1A or RUNX2 amplification and sex, age, histologic cell type, or patient survival.CONCLUSIONS. No copy number changes were associated exclusively with metastatic CoMs. However, further investigation of the role of CDKN1A and RUNX2 in CoMs development and that of MLH1, TIMP2, MGMT, and ECHS1 in metastatic CoMs is warranted. Validation of the observed gene and chromosome arm copy number changes in a larger cohort of primary and metastatic CoMs is necessary to identify the patients at highest risk for CoMs metastasis. (Invest Ophthalmol Vis Sci. 2011;52:5598-5604) DOI:10.1167/iovs.10-6934