Caria Paola, Cantara Silvia, Frau Daniela Virginia, Pacini Furio, Vanni Roberta, Dettori Tinuccia
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato 09042, Italy.
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena 53100, Italy.
Int J Mol Sci. 2016 Oct 21;17(10):1759. doi: 10.3390/ijms17101759.
Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency of () amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL and mutational status. We analyzed gene amplification and the integrity of , , , and genes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzed mutation and RTL by qRT-PCR. Significant amplification ( = 0.0076), which was restricted to scattered groups of cells, was found in fPTC samples. amplification in fPTCs was invariably associated with mutation. RTL was shorter in fPTCs than sPTCs ( < 0.001). No rearrangements of other tested genes were observed. These findings suggest that the association of amplification with mutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy.
大量研究致力于了解散发性和家族性甲状腺乳头状癌是否为不同的生物学实体。我们之前已经证明，家族性甲状腺乳头状癌（fPTC）细胞在血液和组织中均表现出较短的相对端粒长度（RTL），并且这些特征可能与染色体不稳定性有关。在此，我们研究了散发性甲状腺乳头状癌（sPTC）和fPTC中（）扩增以及其他最近报道的基因改变的频率，并评估了与RTL和突变状态的相关性。我们通过荧光原位杂交在13例fPTC和18例sPTC患者的分离细胞核及石蜡包埋的福尔马林固定切片中分析了基因扩增以及、、和基因的完整性。我们通过qRT-PCR分析了突变和RTL。在fPTC样本中发现了显著的扩增（= 0.0076），其仅限于散在的细胞群。fPTC中的扩增总是与突变相关。fPTC中的RTL比sPTC中的短（< 0.001）。未观察到其他测试基因的重排。这些发现表明，扩增与突变以及端粒缩短之间的关联可能代表肿瘤侵袭性的一个标志物，并且在难治性甲状腺癌中，可能值得探索作为靶向治疗的位点。
