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新型及已建立的人间变性甲状腺癌模型的分子细胞遗传学特征

Molecular cytogenetic profiles of novel and established human anaplastic thyroid carcinoma models.

作者信息

Lee Jia-Jing, Foukakis Theodoros, Hashemi Jamileh, Grimelius Lars, Heldin Nils-Erik, Wallin Göran, Rudduck Christina, Lui Weng-Onn, Höög Anders, Larsson Catharina

机构信息

Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital-Solna, Sweden.

出版信息

Thyroid. 2007 Apr;17(4):289-301. doi: 10.1089/thy.2006.0246.

Abstract

In this study we present two novel anaplastic thyroid carcinoma (ATC) lines (HTh 104 and HTh 112) and further characterize six frequently used ATC lines (HTh 7, HTh 74, HTh 83, C 643, KAT-4, and SW 1736). Three of the lines carried a heterozygous BRAF mutation V600E, which is in line with reports of BRAF mutations in primary ATC and papillary thyroid cancer. Several nonrandom breakpoints were identified by spectral karyotyping (SKY) and G-banding in these lines including the novel 1p36 and 17q24-25 as well as 3p21-22 and 15q26 that are also implicated in well-differentiated thyroid cancers. Comparative genomic hybridization showed frequent gain of 20q, including the UBCH10 gene in 20q13.12, which was further confirmed by array-comparative genomic hybridization and fluorescence in situ hybridization analyses. Our results concur with previous studies in both primary tumors and cell lines, indicating that gain of chromosome 20 is important in the pathogenesis of ATC and/or progression of differentiated thyroid cancers to ATC.

摘要

在本研究中,我们展示了两种新型间变性甲状腺癌(ATC)细胞系(HTh 104和HTh 112),并进一步对六种常用的ATC细胞系(HTh 7、HTh 74、HTh 83、C 643、KAT-4和SW 1736)进行了表征。其中三个细胞系携带杂合性BRAF突变V600E,这与原发性ATC和甲状腺乳头状癌中BRAF突变的报道一致。通过光谱核型分析(SKY)和G显带在这些细胞系中鉴定出了几个非随机断点,包括新发现的1p36和17q24 - 25以及3p21 - 22和15q26,这些断点也与分化型甲状腺癌有关。比较基因组杂交显示20q频繁扩增,包括20q13.12处的UBCH10基因,这通过阵列比较基因组杂交和荧光原位杂交分析得到进一步证实。我们的结果与先前在原发性肿瘤和细胞系中的研究一致,表明20号染色体扩增在ATC发病机制和/或分化型甲状腺癌向ATC进展中起重要作用。

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