Durand Stéphanie, Ferraro-Peyret Carole, Joufre Mireille, Chave Annie, Borson-Chazot Françoise, Selmi-Ruby Samia, Rousset Bernard
Institut National de la Santé et de la Recherche Médicale, UMR 664, Lyon F-69372, France.
Endocr Relat Cancer. 2009 Jun;16(2):467-81. doi: 10.1677/ERC-08-0081. Epub 2009 Feb 10.
About 60-70% of papillary thyroid carcinomas (PTC) present a BRAF(T1799A) gene mutation or a rearrangement of RET gene (RET/PTC). In this study, we examined whether PTC without BRAF(T1799A) mutation and without RET/PTC rearrangement named PTC-ga(-) were distinguishable from PTC-ga(+) (with one or the other gene alteration) on the basis of gene expression characteristics. We analyzed the mutational state of 116 PTC and we compared gene expression profiles of PTC-ga(+) and PTC-ga(-) from data of a 200 gene macroarray and quantitative PCR. Seventy five PTC were PTC-ga(+) and 41 were PTC-ga(-). Unsupervised analyses of macroarray data by hierarchical clustering led to a complete segregation of PTC-ga(+) and PTC-ga(-). In a series of 42 genes previously recognized as PTC 'marker' genes, 22 were found to be expressed at a comparable level in PTC-ga(-) and normal tissue. Thyroid-specific genes, TPO, TG, DIO1, and DIO2 were under-expressed in PTC-ga(+) but expressed at a normal level in PTC-ga(-). A few genes including DUOX1 and DUOX2 were selectively dys-regulated in PTC-ga(-). Tumor grade of PTC-ga(-) was lower than that of PTC-ga(+). There was a strong association between the mutational state and histiotype of PTC; 81% of PTC follicular variants were corresponded to PTC-ga(-), whereas 84% of PTC of classical form were PTC-ga(+). In conclusion, we show that PTC without BRAF(T1799A) mutation or RET/PTC rearrangement, mainly corresponding to follicular variants, maintain a thyroid differentiation expression level close to that of normal tissue and should be of better prognosis than PTC with one or the other gene alteration.
约60%-70%的甲状腺乳头状癌（PTC）存在BRAF（T1799A）基因突变或RET基因重排（RET/PTC）。在本研究中，我们检测了无BRAF（T1799A）突变且无RET/PTC重排的PTC（命名为PTC-ga(-)）是否能基于基因表达特征与PTC-ga(+)（存在一种或另一种基因改变）区分开来。我们分析了116例PTC的突变状态，并根据200基因宏阵列和定量PCR数据比较了PTC-ga(+)和PTC-ga(-)的基因表达谱。75例PTC为PTC-ga(+)，41例为PTC-ga(-)。通过层次聚类对宏阵列数据进行无监督分析，导致PTC-ga(+)和PTC-ga(-)完全分离。在先前被认为是PTC“标记”基因的一系列42个基因中，发现22个在PTC-ga(-)和正常组织中的表达水平相当。甲状腺特异性基因TPO、TG、DIO1和DIO2在PTC-ga(+)中表达下调，但在PTC-ga(-)中表达水平正常。包括DUOX1和DUOX2在内的一些基因在PTC-ga(-)中选择性失调。PTC-ga(-)的肿瘤分级低于PTC-ga(+)。PTC的突变状态与组织学类型之间存在很强的关联；81%的PTC滤泡变体对应于PTC-ga(-)，而84%的经典型PTC为PTC-ga(+)。总之，我们表明无BRAF（T1799A）突变或RET/PTC重排的PTC主要对应于滤泡变体，其甲状腺分化表达水平接近正常组织，预后应优于存在一种或另一种基因改变的PTC。
