Chromosome 3 Status Combined With BAP1 and EIF1AX Mutation Profiles Are Associated With Metastasis in Uveal Melanoma

被引:131
作者
Ewens, Kathryn G. [1 ]
Kanetsky, Peter A. [2 ]
Richards-Yutz, Jennifer [1 ]
Purrazzella, Juliana [1 ]
Shields, Carol L. [3 ]
Ganguly, Tapan [4 ]
Ganguly, Arupa [1 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Genet, Genet Diagnost Lab, Philadelphia, PA 19104 USA
[2] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA
[3] Thomas Jefferson Univ, Wills Eye Hosp, Ocular Oncol Serv, Philadelphia, PA 19107 USA
[4] Univ Penn, Perelman Sch Med, DNA Sequencing Facil, Penn Genom Anal Core, Philadelphia, PA 19104 USA
关键词
uveal melanoma; chromosome; 3; somatic mutation; BAP1; EIF1AX; GNAQ; GNA11; SF3B1; DEPENDENT PROBE AMPLIFICATION; MALIGNANT MESOTHELIOMA; SOMATIC MUTATIONS; CHOROIDAL MELANOMAS; CUTANEOUS MELANOMA; SF3B1; PROGNOSIS; CANCER; GNAQ; ABNORMALITIES;
D O I
10.1167/iovs.14-14550
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. Somatic mutations in GNAQ, GNA11, SF3B1, EIF1AX, and BAP1 have been identified in uveal melanoma (UM). The aim of this study was to determine whether mutations in these genes in primary tumors were associated with metastases in individuals diagnosed with UM. METHODS. A total of 63 UM cases who developed a metastasis within 48 months of primary treatment and 53 UM controls who were metastasis-free over a similar time period were selected for the study. Primary UM cases were screened for mutations in GNAQ, GNA11, SF3B1, EIF1AX, and BAP1. The association of these mutations with tumor characteristics, chromosome 3 copy number, and metastatic status was analyzed by logistic regression to estimate the odds of developing metastasis within 48 months. RESULTS. As expected, tumor diameter, thickness, cilio-choroidal location, and chromosome 3 monosomy were all significantly (P < 0.02) associated with the presence of metastasis. In univariate analysis, GNA11 (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-5.5) and BAP1 (OR 6.3, 95% CI 2.7-14.4) mutations were positively associated and EIF1AX mutation (OR 0.13, 95% CI 0.034-0.47) was inversely associated with metastatic status at 48 months after UM treatment. After adjustment for covariates, a chromosome 3 monosomy/BAP1-mutation/EIF1AX-wild-type (WT) mutation profile was strongly associated (OR 37.5, 95% CI 4.3-414) with the presence of metastasis compared with a chromosome 3 disomy/BAP1-WT/EIF1AX mutation profile. CONCLUSIONS. The results suggest that knowledge of mutations in BAP1 and EIF1AX can enhance prognostication of UM beyond that determined by chromosome 3 and tumor characteristics. Tumors with chromosome 3 disomy/BAP1-WT/EIF1AX-WT have a 10-fold increased risk of metastasis at 48 months compared with disomy-3/BAP1-WT/EIF1AX mutant tumors.
引用
收藏
页码:5160 / 5167
页数:8
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