Yoshimoto Maisa, Graham Cassandra, Chilton-MacNeill Susan, Lee Eric, Shago Mary, Squire Jeremy, Zielenska Maria, Somers Gino R
Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Cancer Genet Cytogenet. 2009 Nov;195(1):1-11. doi: 10.1016/j.cancergencyto.2009.06.015.
Pediatric undifferentiated soft tissue sarcomas (USTS) are a diagnostically challenging group of neoplasms. Recently, a subcategory of USTS with primitive round cell morphology and a t(4;19)(q35;q13) rearrangement has been defined. The present study applied high-throughput array comparative genomic hybridization together with spectral karyotyping, four-color fluorescence in situ hybridization (FISH), and reverse transcriptase-polymerase chain reaction (RT-PCR) to a series of three pediatric USTS. Two of these had primitive round cell morphology with CD99 positivity; the third had a spindled and myxoid appearance. By genomic analyses, both primitive round cell sarcomas had t(4;19)(q35;q13) [corrected] rearrangements in addition to several imbalances throughout the genome. Four-color FISH and in silico analyses of the breakpoint region at 19q13 identified the potential involvement of the candidate oncogene CIC. By RT-PCR, fusion transcripts involving CIC (19q13) and DUX4 (4q35) were confirmed to be present in both primitive round cell sarcomas, further defining the breakpoints seen by genomic analysis. Described here are two tumors belonging to the rare category of CIC-DUX4-positive primitive sarcomas, with detailed cytogenetic and genomic information regarding this novel subclass of pediatric malignancy. Molecular and cytogenetic techniques for the detection of the CIC-DUX4 fusion gene are described, to aid in recognition and diagnosis.
小儿未分化软组织肉瘤（USTS）是一组诊断具有挑战性的肿瘤。最近，已定义了一类具有原始圆形细胞形态和t(4;19)(q35;q13)重排的USTS亚类。本研究对一系列3例小儿USTS应用了高通量阵列比较基因组杂交以及光谱核型分析、四色荧光原位杂交（FISH）和逆转录聚合酶链反应（RT-PCR）。其中2例具有原始圆形细胞形态且CD99阳性；第3例具有梭形和黏液样外观。通过基因组分析，2例原始圆形细胞肉瘤除了全基因组的几个失衡外，均有t(4;19)(q35;q13) [校正后]重排。对19q13断点区域的四色FISH和计算机分析确定了候选致癌基因CIC的潜在参与。通过RT-PCR，证实涉及CIC（19q13）和DUX4（4q35）的融合转录本存在于2例原始圆形细胞肉瘤中，进一步明确了基因组分析中所见的断点。本文描述了2例属于罕见的CIC-DUX4阳性原始肉瘤类别的肿瘤，并提供了有关这种小儿恶性肿瘤新亚类的详细细胞遗传学和基因组信息。还描述了检测CIC-DUX4融合基因的分子和细胞遗传学技术，以辅助识别和诊断。
