Molecular assays for chromosomal translocations in the diagnosis of pediatric soft tissue sarcomas.
Molecular assays for chromosomal translocations in the diagnosis of pediatric soft tissue sarcomas.
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DOI：
10.1001/jama.1995.03520310051029
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发表时间：
1995-02
期刊：
影响因子：
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通讯作者：
F. Barr;J. Chatten;C. D’Cruz;Albert E. Wilson;L. Nauta;L. Nycum;J. Biegel;R. Womer
中科院分区：
文献类型：
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作者：
F. Barr;J. Chatten;C. D’Cruz;Albert E. Wilson;L. Nauta;L. Nycum;J. Biegel;R. Womer
目的比较特征性染色体易位分子检测与常规组织病理学和细胞遗传学分析在儿童软组织肉瘤鉴别诊断中的价值。设计与组织病理学诊断的盲法对照。设置三级护理儿童医院。患者共79例软组织肉瘤患者冰冻的肿瘤组织和病理切片可供复习。方法用逆转录聚合酶链式反应检测肿瘤组织中的RNA。在肺泡型横纹肌肉瘤中检测到PAX3-FKHR和PAX7-FKHR嵌合转录本，在尤文肉瘤中检测到EWS-FLI1和EWS-ERG嵌合转录本，在促结缔组织增生性小圆细胞瘤中检测到EWS-WT1嵌合转录本。主要观察指标聚合酶链式反应结果与细胞遗传学和组织病理学结果进行比较。结果这些检测方法在所有标准细胞遗传学发现易位的病例中检测到嵌合转录本，并在细胞遗传学中未发现易位的其他病例中检测到嵌合转录本。21例肺泡型横纹肌肉瘤中有18例存在Pax3-FKHR或PAX7-FKHR融合，30例胚胎型横纹肌肉瘤中有2例Pax3-FKHR融合，7例未分化肉瘤中有1例Pax3-FKHR或PAX7-FKHR融合。8例尤因肉瘤中6例和7例未分化肉瘤中1例检测到EWS-FLI1或EWS-ERG融合。在3例促结缔组织增生性小圆细胞肿瘤中有3例发现了EWS-WT1融合。结论特异性基因融合的分子检测为软组织肉瘤的鉴别诊断提供了一种遗传学方法。遗传分类与标准的组织病理学分类密切对应。聚合酶链式反应分析嵌合转录本是快速和客观评估儿童软组织肉瘤的有用工具。
OBJECTIVE To compare molecular assays for characteristic chromosomal translocations with standard histopathologic and cytogenetic analysis in the differential diagnosis of pediatric soft tissue sarcomas. DESIGN Blinded comparison with histopathologic diagnosis. SETTING Tertiary care children's hospital. PATIENTS A total of 79 soft tissue sarcoma patients with frozen tumor tissue and histopathologic slides available for review. METHODS The RNA from the tumors was assayed by the reverse transcriptase-polymerase chain reaction. These assays detect PAX3-FKHR and PAX7-FKHR chimeric transcripts in alveolar rhabdomyosarcoma, EWS-FLI1 and EWS-ERG chimeric transcripts in Ewing's sarcoma, and EWS-WT1 chimeric transcripts in desmoplastic small round cell tumor. MAIN OUTCOME MEASURES The polymerase chain reaction findings were compared with cytogenetic and histopathologic results. RESULTS These assays detected chimeric transcripts in all cases in which translocations were found by standard cytogenetics as well as additional cases without cytogenetically detectable translocations. PAX3-FKHR or PAX7-FKHR fusions were present in 18 of 21 alveolar rhabdomyosarcomas, two of 30 embryonal rhabdomyosarcomas, and one of seven undifferentiated sarcomas. EWS-FLI1 or EWS-ERG fusions were detected in six of eight Ewing's sarcomas and one of seven undifferentiated sarcomas. The EWS-WT1 fusion was found in three of three desmoplastic small round cell tumors. CONCLUSIONS Molecular assays for specific gene fusions provide a genetic approach to the differential diagnosis of soft tissue sarcomas. The genetic categories correspond closely to the standard histopathologic categories. The polymerase chain reaction assays for chimeric transcripts are useful tools for the rapid and objective assessment of pediatric soft tissue sarcomas.