MOLECULAR CHARACTERIZATION OF SOLID PEDIATRIC TUMORS

(A)横纹肌肉瘤--肺泡型与胚胎型： 肺泡型RMS中一致的t(2；13)(q35；q14)易位导致 PAX3或PAX7基因与FKHR因子的融合。vbl.使用 逆转录-聚合酶链式反应和荧光原位杂交 (FISH)技术，我们将调查PAX3(PAX7)/FKHR的存在 转录本在肺泡型RMS中大量存在。胚胎的均方根 另一只手表现出可复制的染色体物质损失 染色体11p15.5。我们计划使用RFLP和适当的染色体 用探针研究杂合性丢失的频率 人胚胎RMS中存在11p15.5基因的(LOH)。 (B)神经外胚层肿瘤： T(11；22)(q24；q12)和t(21；22)(q22；q12)易位 在外周神经外胚层肿瘤(PNET)家族中， 22号染色体EWS基因与FlI1或erg基因的融合 分别在11号和21号染色体上产生融合转录本 通过RT-PCR可以检测到。我们目前已经分析了50个具有 尤文氏a肉瘤/PNET的推定诊断 RT-PCR检测这些转录本的表达情况。 神经纤维瘤病(NF)1基因被认为是一种可能的 抑癌基因已定位于染色体带17q11.2。呵呵 已报道在恶性神经鞘瘤中存在nf1基因。 但在患有NF1的良性神经纤维瘤中不存在。 此外，22号染色体(q11.3-12)上含有 据报道，NF2基因存在于一名NF1患者的肿瘤中。我们会 进行良性和非小细胞肺癌17、11和22号染色体的杂合性缺失研究 恶性神经外胚层肿瘤(神经鞘和PNET) 散发性和在神经纤维性疾病患者中评估可能的分子 不同之处。

(a)Rhabdomyosarcoma (RMS)-alveolar versus embryonal: A consistent t(2;13)(q35;q14) translocation in alveolar RMS results in fusion between PAX3 or PAX7 genes with the FKHR factors. Using reverse transcription (RT)-PCR and fluorescence in situ hybridization (FISH) technique, we will investigate the presence of PAX3 (PAX7)/FKHR transcripts in a large number of alveolar RMS. Embryonal RMS on the other hand exhibits a reproducible loss of chromosomal material on chromosome 11p15.5. We plan to use RFLP and appropriate chromosomal probes to investigate the frequency by which loss of heterozygosity (LOH) of locus 11p15.5 is encountered in human embryonal RMS. (b)Neuroectodermal tumors: The reciprocal t(11;22)(q24;q12) and t(21;22) (q22;q12) translocations in the family of peripheral neuroectodermal tumors (PNET) result in fusion between the EWS gene in chromosome 22 and the Fli1 or erg genes in chromosomes 11 and 21 respectively generating fusion transcripts detectable by RT-PCR. We have currently analyzed 50 tumors with a presumable diagnosis of Ewing's a sarcoma/PNET for the presence of these transcripts by RT-PCR. The neurofibromatosis (NF)1 gene which is considered to be a possible tumor suppressor gene has been mapped to chromosome band 17q11.2. LOH of the NF1 locus has been reported in a malignant nerve sheath tumor but not in benign neurofibromas from a patient with NF 1. In addition, loss of regions on chromosome 22 (q11.3-12) which harbors the NF2 gene have been reported in tumors from a NF1 patient. We will undertake LOH studies for chromosomes 17, 11 and 22 in benign and malignant neuroectodermal tumors (nerve sheath and PNET) occurring sporadically and in patients with NF to evaluate possible molecular differences.