Copy number alterations determined by single nucleotide polymorphism array testing in the clinical laboratory are indicative of gene fusions in pediatric cancer patients
Copy number alterations determined by single nucleotide polymorphism array testing in the clinical laboratory are indicative of gene fusions in pediatric cancer patients
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DOI：
10.1002/gcc.22477
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发表时间：
2017-10-01
影响因子：
3.7
通讯作者：
Biegel, Jaclyn A.
中科院分区：
文献类型：
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作者：
Busse, Tracy M.;Roth, Jacquelyn J.;Biegel, Jaclyn A.
由结构重排引起的基因融合是儿童肿瘤发生的一种既定机制。在这个临床队列中，来自1211名儿童癌症患者的1,350个基于单核苷酸多态性（SNP）的染色体微阵列被评估与基因融合相关的拷贝数改变（CNAs）。42%的患者进行了核型或荧光原位杂交研究。10%的骨髓或实体瘤标本具有SNP阵列相关的CNAs，提示基因融合。在骨髓样本中检测到涉及ETV6、ABL1-NUP214、EBF1-PDGFRB、KMT2A（MLL）、LMO2-RAG、MYH11-CBFB、NSD1-NUP98、PBX1、STIL-TAL1、ZNF384-TCF3、P2RY8-CRLF2和RUNX1T1-RUNX1融合体的改变。低级别胶质瘤中最常见的改变是7q34串联重复，导致KIAA1549-BRAF融合。在儿童脑肿瘤中发现的其他融合包括FAM131B-BRAF和RAF1-QKI。COL1A1-PDGFB、CRTC1-MAML2、EWSR1、HEY1、pax3、PAX7-FOXO1和PLAG1融合在多种实体瘤中被检测到，在动脉瘤性骨囊肿中检测到一种新的潜在基因融合FGFR1-USP6。这些基因融合体的鉴定有助于肿瘤的诊断。成人血液病和实体瘤主要由突变驱动，而儿童血液病和实体瘤主要以CNAs和基因融合为特征。因此，染色体微阵列分析是一个在临床环境中识别诊断和预后标记的强大平台。
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion. Alterations involving ETV6, ABL1-NUP214, EBF1-PDGFRB, KMT2A(MLL), LMO2-RAG, MYH11-CBFB, NSD1-NUP98, PBX1, STIL-TAL1, ZNF384-TCF3, P2RY8-CRLF2, and RUNX1T1-RUNX1 fusions were detected in the bone marrow samples. The most common alteration among the low-grade gliomas was a 7q34 tandem duplication resulting in a KIAA1549-BRAF fusion. Additional fusions identified in the pediatric brain tumors included FAM131B-BRAF and RAF1-QKI. COL1A1-PDGFB, CRTC1-MAML2, EWSR1, HEY1, PAX3-and PAX7-FOXO1, and PLAG1 fusions were determined in a variety of solid tumors and a novel potential gene fusion, FGFR1-USP6, was detected in an aneurysmal bone cyst. The identification of these gene fusions was instrumental in tumor diagnosis. In contrast to hematologic and solid tumors in adults that are predominantly driven by mutations, the majority of hematologic and solid tumors in children are characterized by CNAs and gene fusions. Chromosomal microarray analysis is therefore a robust platform to identify diagnostic and prognostic markers in the clinical setting.