PDF(Pubmed)
Abstract：
UNASSIGNED: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group.
UNASSIGNED: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates.
UNASSIGNED: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018).
UNASSIGNED: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).
UNASSIGNED: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates.
UNASSIGNED: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018).
UNASSIGNED: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).
摘要：
■为了探索儿童和年轻人脉络膜和睫状体黑色素瘤的遗传背景，特别关注该年龄组的BAP1种系变异。
■25岁以下确诊为脉络膜或睫状体黑色素瘤的患者被纳入本回顾性研究，多中心观察研究。核BAP1免疫阳性用于评估肿瘤中功能性BAP1的存在。使用IonTorrent平台的下一代测序用于确定BAP1，EIF1AX，SF3B1、GNAQ和GNA11及3号染色体在肿瘤中的地位或在从血液或唾液中提取的DNA中的地位。使用Kaplan-Meier估计分析生存率。
■诊断时的平均年龄为17岁（范围5.0-24.8）。在一名18岁的患者中发现了种系BAP1致病性变异，和一个体细胞变体，主要基于免疫组织化学，在31个可用标本中的13个（42%）。一个肿瘤具有体细胞SF3B1致病变体。Disomy3和肿瘤中BAP1致病性变体的缺失预测了最长的无转移生存期。男性无转移生存期长于女性(P=0.018)。
■我们没有发现与成人相比，儿童和年轻人的脉络膜和睫状体黑色素瘤的BAP1种系易感性高于平均水平。男性具有更有利的存活和二体3,并且在肿瘤组织中不存在BAP1突变预测最有利的无转移存活。在一名患者（1％）中鉴定出BAP1种系致病变异，和主要基于免疫组织化学的体细胞变异13（42％）。
■25岁以下确诊为脉络膜或睫状体黑色素瘤的患者被纳入本回顾性研究，多中心观察研究。核BAP1免疫阳性用于评估肿瘤中功能性BAP1的存在。使用IonTorrent平台的下一代测序用于确定BAP1，EIF1AX，SF3B1、GNAQ和GNA11及3号染色体在肿瘤中的地位或在从血液或唾液中提取的DNA中的地位。使用Kaplan-Meier估计分析生存率。
■诊断时的平均年龄为17岁（范围5.0-24.8）。在一名18岁的患者中发现了种系BAP1致病性变异，和一个体细胞变体，主要基于免疫组织化学，在31个可用标本中的13个（42%）。一个肿瘤具有体细胞SF3B1致病变体。Disomy3和肿瘤中BAP1致病性变体的缺失预测了最长的无转移生存期。男性无转移生存期长于女性(P=0.018)。
■我们没有发现与成人相比，儿童和年轻人的脉络膜和睫状体黑色素瘤的BAP1种系易感性高于平均水平。男性具有更有利的存活和二体3,并且在肿瘤组织中不存在BAP1突变预测最有利的无转移存活。在一名患者（1％）中鉴定出BAP1种系致病变异，和主要基于免疫组织化学的体细胞变异13（42％）。
