Aschero Rosario, Francis Jasmine H, Ganiewich Daiana, Gomez-Gonzalez Soledad, Sampor Claudia, Zugbi Santiago, Ottaviani Daniela, Lemelle Lauriane, Mena Marcela, Winter Ursula, Correa Llano Genoveva, Lamas Gabriela, Lubieniecki Fabiana, Szijan Irene, Mora Jaume, Podhajcer Osvaldo, Doz François, Radvanyi François, Abramson David H, Llera Andrea S, Schaiquevich Paula S, Lavarino Cinzia, Chantada Guillermo L
Pathology Service, Hospital de Pediatría JP Garrahan, Buenos Aires 1245, Argentina.
National Scientific and Technical Research Council, CONICET, Buenos Aires 1425, Argentina.
Cancers (Basel). 2021 Feb 8;13(4):673. doi: 10.3390/cancers13040673.
Most reports about copy number alterations (CNA) in retinoblastoma relate to patients with intraocular disease and features of children with extraocular relapse remain unknown, so we aimed to describe the CNA in this population. We evaluated 23 patients and 27 specimens from 4 centers. Seventeen cases had extraocular relapse after initial enucleation and six cases after an initial preservation attempt. We performed an analysis of CNA and gene alteration by SNP array (Single Nucleotide Polymorfism array), whole-exome sequencing, IMPACT panel and CGH array (Array-based comparative genomic hybridization). All cases presented CNA at a higher prevalence than those reported in previously published studies for intraocular cases. CNA previously reported for intraocular retinoblastoma were found at a high frequency in our cohort: gains in 1q (69.5%), 2p (60.9%) and 6p (86.9%), and 16q loss (78.2%). Other, previously less-recognized, CNA were found including loss of 11q (34.8%), gain of 17q (56.5%), loss of 19q (30.4%) and alterations were present in 72.7% of our cases. A high number of CNA including 11q deletions, 17q gains, 19q loss, and alterations, are more common in extraocular retinoblastoma. Identification of these features may be correlated with a more aggressive tumor warranting consideration for patient management.
大多数关于视网膜母细胞瘤拷贝数改变（CNA）的报告都与眼内疾病患者有关，而眼外复发儿童的特征尚不清楚，因此我们旨在描述这一人群中的CNA情况。我们评估了来自4个中心的23例患者和27份标本。17例患者在初次眼球摘除术后出现眼外复发，6例在初次尝试保留眼球后出现复发。我们通过单核苷酸多态性阵列（SNP阵列）、全外显子测序、IMPACT检测板和基于阵列的比较基因组杂交（CGH阵列）对CNA和基因改变进行了分析。所有病例中CNA的发生率均高于先前发表的眼内病例研究报告中的发生率。我们的队列中发现先前报道的眼内视网膜母细胞瘤的CNA出现频率较高：1q增益（69.5%）、2p增益（60.9%）和6p增益（86.9%）以及16q缺失（78.2%）。还发现了其他先前较少被认识的CNA，包括11q缺失（34.8%）、17q增益（56.5%）、19q缺失（30.4%），并且72.7%的病例存在改变。大量的CNA，包括11q缺失、17q增益、19q缺失以及改变，在眼外视网膜母细胞瘤中更为常见。识别这些特征可能与更具侵袭性的肿瘤相关，值得在患者管理中予以考虑。
