Dockhorn-Dworniczak B, Schäfer K L, Blasius S, Christiansen H, Koscielniak E, Ritter J, Winkelmann W, Jürgens H, Böcker W
Gerhard-Domagk-Institut für Pathologie, Münster.
Klin Padiatr. 1997 Jul-Aug;209(4):156-64. doi: 10.1055/s-2008-1043964.
Recent studies have shown that many types of soft-tissue sarcomas are characterized by specific chromosomal translocations, which are likely to be of etiologic significance. In order to evaluate their diagnostic impact, a panel of 129 sarcomas comprising 78 Ewing's tumors (ET), 19 rhabdomyosarcomas (RMS), 20 neuroblastomas (NB), 9 synovialsarcomas, 2 esthesioneuroblastomas, and 1 desmoplastic small-round-cell tumor (DSRCT) were analysed for the occurrence of the major recurrent translocations, such as t(11;22)(q24;q12), t(21;22)(q22;q12), t(11;22)(p13;q12), t(2;13)(q35;q14), t(1;13)(p36;q14), and t(X;18)(p11;q11).
Nitrogen-frozen tissue material was analysed by means of Reverse Transcription followed by PCR (Polymerase-Chain Reaction) and nested PCR (RT-PCR). Specificity of the PCR products obtained was confirmed by non-isotopic Southern-Blot analysis with gene-specific probes and/or automated direct sequence analysis.
75 ETs have been shown to carry either a t(11;22) or t(21;22) translocation by identification of chimeric EWS-FLI-1 or EWS-ERG gene-fusion transcripts respectively. 3 ETs were lacking EWS/FLI-1 or EWS-ERG fusion products. 2 of these tumors were shown on review to have unusual morphological features for ETs. 8/19 RMS were initially diagnosed as alveolar RMS. These tumours were shown to carry either a t(2;13) translocation exhibiting chimeric PAX3-FKHR fusion transcripts or a t(1;13) translocation with PAX7-FKHR chimeric gene products. One RMS of the embryonal group also carried a t(1;13) translocation. Reevaluation demonstrated a partly alveolar morphology. In 8/9 synovial sarcomas a t(X;18) translocation was identified. Expression of a EWS-WTI gene-fusion product associated with a t(11;22) translocation was found in the DSRCT. None of these rearrangements were detected in the NBs and 2 esthesioneuroblastomas.
Our results support the concept that the major recurrent translocations are histogenetically specific for a subset of sarcomas. Thus, the detection of tumor type-specific translocations represents an extremely useful diagnostic modality as an adjunct to surgical pathology.
最近的研究表明，许多类型的软组织肉瘤具有特定的染色体易位特征，这可能具有病因学意义。为了评估其诊断价值，对一组129例肉瘤进行了分析，其中包括78例尤因肉瘤（ET）、19例横纹肌肉瘤（RMS）、20例神经母细胞瘤（NB）、9例滑膜肉瘤、2例嗅神经母细胞瘤和1例促纤维组织增生性小圆细胞肿瘤（DSRCT），以检测主要复发性易位的发生情况，如t(11;22)(q24;q12)、t(21;22)(q22;q12)、t(11;22)(p13;q12)、t(2;13)(q35;q14)、t(1;13)(p36;q14)和t(X;18)(p11;q11)。
采用逆转录聚合酶链反应（RT-PCR）和巢式PCR对液氮冷冻的组织材料进行分析。通过使用基因特异性探针的非同位素Southern杂交分析和/或自动直接序列分析来确认所获得的PCR产物的特异性。
通过分别鉴定嵌合的EWS-FLI-1或EWS-ERG基因融合转录本，已证实75例ET携带t(11;22)或t(21;22)易位。3例ET缺乏EWS/FLI-1或EWS-ERG融合产物。经复查，其中2例肿瘤具有ET不常见的形态学特征。19例RMS中有8例最初被诊断为肺泡型RMS。这些肿瘤显示携带t(2;13)易位，表现为嵌合的PAX3-FKHR融合转录本，或携带t(1;13)易位，具有PAX7-FKHR嵌合基因产物。1例胚胎型RMS也携带t(1;13)易位。重新评估显示部分为肺泡形态。9例滑膜肉瘤中有8例鉴定出t(X;18)易位。在DSRCT中发现了与t(11;22)易位相关的EWS-WTI基因融合产物的表达。在NB和2例嗅神经母细胞瘤中未检测到这些重排。
我们的结果支持这样的概念，即主要复发性易位在组织发生学上对一部分肉瘤具有特异性。因此，检测肿瘤类型特异性易位作为外科病理学的辅助手段是一种极其有用的诊断方法。
