A cytogenetic and molecular study for improving the quality of the pathologic diagnosis of soft tissue tumors

提高软组织肿瘤病理诊断质量的细胞遗传学和分子研究

• 批准号: 12670181
• 负责人: IWASAKI Hiroshi
• 金额: $ 2.11万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670181/
• 关键词: Soft tissue tumors; Sarcomas; Chromosomes; Cytogenetic analysis; Genetic abnormalities; Chimeric genes; Neurofibromatosis; NF1; 染色体異常; 遺伝子診断; FISH; RT-PCR; CGH; 病理診断

The purpose of this study is to obtain cytogenetic and molecular data useful for the improvement of the diagnosis and differential diagnosis of soft tissue tumors.Results. (1) By using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), we demonstrated that the ring chromosome in Bednar tumor is composed of amplified material from chromosomes 17 and 22. (2) Although histopathological differentiation between dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) is often difficult, our CGH analysis demonstrated that the overrepresentation of 17q and 22q sequences was a common finding in DFSP but not in DF. Thus, CGH seems to be useful for distinguishing DFSP from DF. (3) A microbeam microdissection and nested RT-PCR applied on paraffin-embedded tissue of synovial sarcomas showed that SYT-SSX fusion transcript was detected in both epithelial and spindle cell components of biphasic synovial sarcomas, but not in the control tissue. Our results con … More firm that the synovial sarcoma is of monoclonal origin. (4) CGH was used to detect changes in relative chromosome copy number in 50 cases of peripheral nerve sheath tumors (PNSTs). In NF1-associated neurofibromas, most frequent losses were found in chromosomes 17 [17p11.2-p13 in 9 cases (60%); 17q24-25 in 6 cases (40%)] and 19 [19p13.2 in 8 cases (53%); 19q13.2-qter in 8 cases (53%)], whereas in sporadic neurofibromas and schwannomas, losses of chromosomes 17 and 19 were detected in less than 50% of cases. NF1-associated MPNSTs exhibited gains of chromosomes 17q and X (2/4 cases each), whereas sporadic MPNSTs showed gains of chromosome 4q (3/5 cases). (5) In 27 elastofibromas analyzed by comparative genomic hybridization, the most common recurrent gains were found at chromosomal locations Xq12-q22. The chromosomal region possibly contain genes involved in the development of at least some elastofibromas. (6) we established a new human cell line, JN-DSRCT-1, from a 7-year-old boy with desmoplastic small round cell tumor (DSRCT). The cultured cells exhibited a pathognomonic t(11;22)(p13;p12) and a chimeric transcriptional message of the Ewing's sarcoma gene exon 10 fused to the Wilms' tumor gene exon 8. This cell line will be useful for a variety of important studies such as the pathogenic mechanism, biologic behavior, and therapeutic model of human DSRCT. Less

本研究的目的是获得有助于提高软组织肿瘤诊断和鉴别诊断的细胞遗传学和分子生物学数据。(1)通过荧光原位杂交（FISH）和比较基因组杂交（CGH），我们证明贝德纳尔肿瘤中的环形染色体由来自17号和22号染色体的扩增物质组成。(2)虽然隆突性皮肤纤维肉瘤（DFSP）和皮肤纤维瘤（DF）之间的组织病理学鉴别往往是困难的，我们的CGH分析表明，17 q和22 q序列的过度表达是一个共同的发现，在DFSP，而不是在DF。因此，计算全息图似乎是有用的区分DFSP DF。(3)滑膜肉瘤石蜡包埋组织的微束显微切割和巢式RT-PCR表明，SYT-SSX融合转录本检测到上皮和梭形细胞成分的双相滑膜肉瘤，但在对照组织中没有。我们的结果是， ...更多信息 证实滑膜肉瘤是单克隆起源的。(4)应用CGH检测50例周围神经鞘瘤（PNST）染色体相对拷贝数的变化。在NF 1相关的神经纤维瘤中，最常见的丢失发生在17号染色体[17 p11.2-p13 9例（60%）; 17 q24 -25 6例（40%）]和19号染色体[19 p13.2 8例（53%）; 19q13.2-qter在8例（53%），而在散发性神经纤维瘤和神经鞘瘤，17和19号染色体的损失被检测到在不到50%的情况下。NF 1相关的MPNST表现出染色体17 q和X的增加（各2/4例），而散发的MPNST表现出染色体4 q的增加（3/5例）。(5)在27个弹性纤维瘤比较基因组杂交分析，最常见的复发收益被发现在染色体位置Xq 12-q22。染色体区域可能含有至少参与某些弹性纤维瘤发展的基因。(6)我们建立了一个新的人类细胞系，JN-DSRCT-1，来自一个患有促纤维增生性小圆细胞肿瘤（DSRCT）的7岁男孩。培养的细胞表现出特异性t（11;22）（p13;p12）和尤文氏肉瘤基因外显子10融合到肾母细胞瘤基因外显子8的嵌合转录信息。该细胞株的建立为进一步研究DSRCT的发病机制、生物学行为和治疗模型奠定了基础。少

项目成果

Nishio J, Iwasaki H, Ohjimi Y, Ishiguro M, Koga T, Isayama T, Naito M, Kikuchi M.: "Gain of Xq detected by comparative genomic hybridization in elastofibroma"Int J Mol Med. 10. 277-280 (2002)

Nishio J、Iwasaki H、Ohjimi Y、Ishiguro M、Koga T、Isayama T、Naito M、Kikuchi M.：“通过比较基因组杂交在弹纤维瘤中检测到 Xq 的增益”Int J Mol Med。

Nishio, J., Iwasaki, H., Ohjimi, Y., Ishiguro, M., Isayama, T.et al.: "Supernumerary ring chromosomes in dermatofibrosarcoma protuberans may contain sequences from 8q11.2 approximately qter and 17q21 approximately qter.・・・"Cancer Genet Cytogenet. 129(2).

Nishio, J.、Iwasaki, H.、Ohjimi, Y.、Ishiguro, M.、Isayama, T.等人：“隆起性皮肤纤维肉瘤中的多余环染色体包含来自 8q11.2 大约四分之一和 17q21 大约四分之一的序列。・・・“癌症基因Cytogenet。129(2)。

Yamakawa, K., Iwasaki, H., Ohjimi, Y., Kikuchi, M., Iwashita, A.et al.: "Tumoral calcium pyrophosphate dihydrate crystal deposition disease. A clinicopathologic analysis of five cases"Pathol Res Pract. 197(7). 499-506 (2001)

Yamakawa, K.、Iwasaki, H.、Ohjimi, Y.、Kikuchi, M.、Iwashita, A.等：“肿瘤二水焦磷酸钙晶体沉积病。五例临床病理分析”Pathol Res Pract。

Nishio J, Iwasaki H, Ohjimi Y, Ishiguro M.: "Overrepresentation of 17q22-qter and 22q13 in dermatofibrosarcoma protuberans but not in dermatofibroma : a comparative genornic hybridization study"Cancer Genet Cytogenet. 132. 102-108 (2002)

Nishio J、Iwasaki H、Ohjimi Y、Ishiguro M.：“17q22-qter 和 22q13 在隆突性皮肤纤维肉瘤中的过度表达，但在皮肤纤维瘤中没有：比较基因组杂交研究”癌症基因细胞遗传学。

Nishio J, Iwasaki H, Ishiguro M, Ohjimi Y, Fujita C, Yanai F, Nibu K, Mitsudome A, Kaneko Y: "Establishment and characterization of a novel human desmoplastic small round cell tumor cell line JN-DSRCT-1"Lab Invest. 82. 1175-1182 (2002)

Nishio J、Iwasaki H、Ishiguro M、Ohjimi Y、Fujita C、Yanai F、Nibu K、Mitsudome A、Kaneko Y：“新型人类促结缔组织增生性小圆细胞肿瘤细胞系 JN-DSRCT-1 的建立和表征”实验室投资