Akhavanfard Sara, Nohr Erik, AlNajjar Mohammad, Haughn Mollie, Hashimoto Sayaka, Deeg Carol, Pfau Ruthann, Brundler Marie-Anne, Reshmi Shalini C
Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Department of Pathology and Laboratory Medicine, Alberta Children's Hospital, Calgary, Alberta, Canada.
Case Rep Oncol. 2021 Mar 23;14(1):585-591. doi: 10.1159/000512187. eCollection 2021 Jan-Apr.
Neuroblastoma is the most common cancer in infants younger than 12 months of age, occurring with an incidence of 1 in 100,000 children. The clinical outcome of neuroblastoma ranges from spontaneous regression to treatment-resistant progression and/or metastasis, and accounts for 8-10% of childhood cancer deaths. Segmental chromosomal aberrations, as well as and amplification, are among factors contributing to an unfavorable genomic profile and high-risk disease classification. Here, we describe a 5-year-old male who presented with a large right renal neuroblastoma tumor having lung and liver metastases. Fluorescence in situ hybridization analysis indicated the presence of >20 copies of the 5' region of the gene in 26% of cells examined. Subsequent copy number assessment did not confirm amplification, but revealed a gain of exons 2-5 of , consistent with increased copy number for the 5' region of the gene. Subsequent array analysis showed the presence of other unfavorable prognostic genomic features, including segmental gain of the 17q region and amplification of the long arm of chromosome 12 harboring and both reported to be poor prognostic indicators in patients with atypical clinical features in neuroblastoma. Taken together, this report illustrates the importance of careful interpretation of aberrant FISH findings and subsequent use of orthogonal methods to clarify the presence of genomic alterations to successfully determine potential treatment targets.
神经母细胞瘤是12个月以下婴儿最常见的癌症，发病率为每10万名儿童中有1例。神经母细胞瘤的临床结果从自发消退到治疗抵抗性进展和/或转移不等，占儿童癌症死亡人数的8-10%。节段性染色体畸变以及 和 扩增是导致不良基因组特征和高危疾病分类的因素之一。在此，我们描述了一名5岁男性，他患有巨大的右肾神经母细胞瘤，伴有肺和肝转移。荧光原位杂交分析表明，在26%的检测细胞中存在>20个 基因5'区域的拷贝。随后的拷贝数评估未证实 扩增，但显示 外显子2-5的增加，与 基因5'区域的拷贝数增加一致。随后的阵列分析显示存在其他不良预后基因组特征，包括17q区域的节段性增加以及12号染色体长臂的扩增，其中 和 均被报道为神经母细胞瘤非典型临床特征患者的不良预后指标。综上所述，本报告说明了仔细解读异常荧光原位杂交结果以及随后使用正交方法来阐明基因组改变的存在对于成功确定潜在治疗靶点的重要性。
