初步分析视网膜母细胞瘤患者房水及肿瘤组织中的基因组信息的一致性。

选取两例经保眼治疗失败行眼球摘除的患儿，对其房水的游离DNA（cell-free DNA，cfDNA）以及肿瘤组织的基因组DNA（genomics DNA，gDNA）采用超低深度全基因组测序（ultra low flux whole genome sequencing，ulf-wgs）和基于隐马尔可夫模型的ichorCNA软件，分析体细胞染色体拷贝数变异（somatic chromosomal copy-number alterations，SCNA）和肿瘤比例（tumor fraction，TF）情况。

实验获得两例病例质量良好的肿瘤组织gDNA、房水样本cfDNA。分析显示4例样本的肿瘤分数均大于10%，可灵敏反映样本的SCNA情况。两例病例的房水样本中，最常见的拷贝数增加区域包括1q、6p和13q，最常见的拷贝缺失区域包括6q和8p。病例1患者房水和肿瘤样本的SCNA区域高度一致，均出现1q、6p以及13号和18号染色体的扩增，6q及8p的拷贝数缺失。病例2患儿的房水在1p、6q、8p和13q区域都显示SCNA变异。

房水活检及经济的ulf-wgs有望成为视网膜母细胞瘤疗效评估和预后的新标准。

Preliminary analysis of the consistency of genomic information in aqueous humor and tumor tissue from patients with Retinoblastoma.

The aqueous humor and tumor tissues of two cases of failed eye protection treatment were selected for this study. Detected by ultra low flux whole genome sequencing (ulf-wgs) and a Hidden Markov model (HMM) based on software-ichorCNA, the genomics DNA (gDNA) of tumor tissues, and cell-free DNA (cfDNA) of the aqueous humor and vitreous were detected. The tumor fraction (TF) and somatic chromosomal copy-number alterations (SCNA) were analyzed.

We archived qualified genomic DNA (gDNA) of tumor samples and cell-free DNA (cfDNA) of aqueous humor samples in both cases. TF of 4 samples were more than 10%. For the aqueous humor of selected two patients, the most frequent copy gain genomic regions included 1q, 6p, and 13q and the most frequent copy loss genomic regions included 6q and 8p. For one patient, we observed the high consistency SCNA between vitreum and tumor, the CNA profiles demonstrated increased chromosomal alterations in chromosomes 1q, 6p, 13 and 18, and decreased chromosomal alterations in chromosomes 6q and 8p. For the other patient, we observed SCNA in aqueous humor, including gain of 1p, 6q, and 13q, and loss of 8p.

Aqueous humor biopsies and technology of ulf-wgs are expected to become the new standard for evaluating the efficacy and prognosis of retinoblastoma.