PDF(Pubmed)
Abstract：
UNASSIGNED: The objective of this study was to report the clinicopathologic features of three cases of MYCN-amplified retinoblastoma identified genetically by aqueous humor sampling.
UNASSIGNED: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data.
UNASSIGNED: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression.
UNASSIGNED: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation.
UNASSIGNED: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.
UNASSIGNED: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data.
UNASSIGNED: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression.
UNASSIGNED: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation.
UNASSIGNED: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.
摘要：
■本研究的目的是报告3例通过房水取样遗传鉴定的MYCN扩增的视网膜母细胞瘤的临床病理特征。
使用来自3名视网膜母细胞瘤患者的房水的分离的无细胞DNA(cfDNA)进行全基因组测序。我们分析了基因组拷贝数和突变改变，组织学和病理特征，和临床数据。
■在这三个视网膜母细胞瘤病例中发现的最常见的遗传改变是2p的局灶性MYCN扩增。所有肿瘤均显示诊断年龄较早，中位数为9个月。肿瘤的组织病理学特征包括病例1中的新生血管形成和视网膜下种植，病例2中的弥漫性脉络膜和椎板前视神经浸润，病例3中的玻璃体完全种植。病例1表达RB蛋白，无RB1突变，病例2不表达RB蛋白，有RB1突变，病例3不表达RB蛋白，可能对RB表达有表观遗传影响。
■我们的报告显示，在4个月至18个月大的患者中诊断出3例单侧视网膜母细胞瘤。来自AHcfDNA的基因组分析显示MYCN扩增在病例1中具有完整的RB蛋白染色,并且在病例2和3中缺乏RB染色。AH中的RB1突变分析证实了病例2中的致病性变异。临床病理显示需要积极治疗的特征，特别是摘除。
■MYCN扩增的视网膜母细胞瘤表现出独特的发病机制和攻击行为，无论MYCN是疾病的主要还是次要驱动因素。当决定去核而不是保守治疗时，来自房水的基因组分析可能是有用的。就靶向治疗而言，2p上的局灶性MYCN扩增可能与视网膜母细胞瘤群体的该子集的肿瘤生长有关。
使用来自3名视网膜母细胞瘤患者的房水的分离的无细胞DNA(cfDNA)进行全基因组测序。我们分析了基因组拷贝数和突变改变，组织学和病理特征，和临床数据。
■在这三个视网膜母细胞瘤病例中发现的最常见的遗传改变是2p的局灶性MYCN扩增。所有肿瘤均显示诊断年龄较早，中位数为9个月。肿瘤的组织病理学特征包括病例1中的新生血管形成和视网膜下种植，病例2中的弥漫性脉络膜和椎板前视神经浸润，病例3中的玻璃体完全种植。病例1表达RB蛋白，无RB1突变，病例2不表达RB蛋白，有RB1突变，病例3不表达RB蛋白，可能对RB表达有表观遗传影响。
■我们的报告显示，在4个月至18个月大的患者中诊断出3例单侧视网膜母细胞瘤。来自AHcfDNA的基因组分析显示MYCN扩增在病例1中具有完整的RB蛋白染色,并且在病例2和3中缺乏RB染色。AH中的RB1突变分析证实了病例2中的致病性变异。临床病理显示需要积极治疗的特征，特别是摘除。
■MYCN扩增的视网膜母细胞瘤表现出独特的发病机制和攻击行为，无论MYCN是疾病的主要还是次要驱动因素。当决定去核而不是保守治疗时，来自房水的基因组分析可能是有用的。就靶向治疗而言，2p上的局灶性MYCN扩增可能与视网膜母细胞瘤群体的该子集的肿瘤生长有关。
