Laboratory of Functional Genomics, Biological Research Centre, Hungarian Academy of Sciences, P.O. Box 521, Szeged, 6701, Hungary.
Pathol Oncol Res. 2012 Apr;18(2):449-58. doi: 10.1007/s12253-011-9467-7. Epub 2011 Dec 11.
Papillary thyroid carcinoma (PTC) is the most common well-differentiated thyroid cancer. Although the great majority of the cases exhibit an indolent clinical course, some of them develop local invasion with distant metastasis, and a few cases transform into undifferentiated/anaplastic thyroid carcinoma with a rapidly lethal course. To identify gene copy number alterations predictive of metastatic potential or aggressive transformation, array-based comparative genomic hybridization (CGH-array) was performed in 43 PTC cases. Formalin-fixed and paraffin-embedded samples from primary tumours of 16 cases without metastasis, 14 cases with only regional lymph node metastasis, and 13 cases with distant metastasis, recurrence or extrathyroid extension were analysed. The CGH-array and confirmatory quantitative real-time PCR results identified the deletion of the EIF4EBP3 and TRAK2 gene loci, while amplification of thymosin beta 10 (TB10) and Tre-2 oncogene regions were observed as general markers for PTC. Although there have been several studies implicating TB10 as a specific marker based on gene expression data, our study is the first to report on genomic amplification. Although no significant difference could be detected between the good and bad prognosis cases in the A-kinase anchor protein 13 (AKAP13) gene region, it was discriminative markers for metastasis. Amplification in the AKAP13 region was demonstrated in 42.9% and 15.4% of the cases with local or with distant metastasis, respectively, while no amplification was detected in non-metastatic cases. AKAP13 and TB10 regions may represent potential new genomic markers for PTC and cancer progression.
甲状腺乳头状癌 (PTC) 是最常见的分化良好的甲状腺癌。尽管绝大多数病例表现出惰性的临床病程，但其中一些病例会发生局部侵犯和远处转移，少数病例会转化为未分化/间变性甲状腺癌，病程迅速致命。为了确定预测转移潜能或侵袭性转化的基因拷贝数改变，对 43 例 PTC 病例进行了基于阵列的比较基因组杂交 (CGH-array)。对来自无转移的 16 例原发性肿瘤、仅有区域淋巴结转移的 14 例和有远处转移、复发或甲状腺外扩展的 13 例的福尔马林固定和石蜡包埋样本进行了分析。CGH-array 和确认性实时定量 PCR 结果鉴定出 EIF4EBP3 和 TRAK2 基因座的缺失，而胸苷酸合成酶 β10 (TB10) 和 Tre-2 癌基因区域的扩增被观察为 PTC 的一般标志物。尽管有几项研究根据基因表达数据表明 TB10 是一种特异性标志物，但我们的研究是第一个报告基因组扩增的研究。尽管在 A-激酶锚蛋白 13 (AKAP13) 基因区域中，在预后良好和不良的病例之间没有发现显著差异，但它是转移的区分性标志物。局部转移病例中 AKAP13 区域的扩增率为 42.9%，远处转移病例中为 15.4%，而无转移病例中未检测到扩增。AKAP13 和 TB10 区域可能是 PTC 和癌症进展的潜在新基因组标志物。
