Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer
Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer
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DOI：
10.1038/sj.onc.1207980
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发表时间：
2004-09-23
期刊：
影响因子：
8
通讯作者：
Greco, A
中科院分区：
文献类型：
--
作者：
Frattini, M;Ferrario, C;Greco, A
甲状腺乳头状癌（PTC）与RET和NTRK1重排和BRAF突变相关。从意大利患者的一个单一中心收集的一系列60个PTC进行组织学重新检查，并细分为分化良好或高细胞变异。通过DNA或cDNA扩增，然后进行自动测序，分析样本采集中是否存在所有报告的PTC相关遗传变异。BRAF基因第11、15外显子的突变率为32%，与PTC高细胞变异有显著相关性。分别在33%和5%的病例中发现RET和NTRK1受体的致癌性重排。未检测到Ras突变。总体而言，在三分之二的样本中检测到遗传改变，并且在任何单一情况下都没有同时发现一个以上的突变事件。基因表达pro.使用cDNA微阵列芯片对31个肿瘤的亚组进行的测序显示，不同病例之间的总体基因表达没有明显差异。然而，对获得的数据进行监督分析，发现了携带BRAF突变或RTK重排的肿瘤中差异表达的基因子集。
Papillary thyroid carcinoma (PTC) is associated with RET and NTRK1 rearrangements and BRAF mutations. A series of 60 PTCs collected in a single center from Italian patients were histologically re-examined and subclassified as well differentiated or tall cell variant. The sample collection was analysed for the presence of all the reported PTC-associated genetic alterations through DNA or cDNA amplification, followed by automated sequencing. The analysis of exons 11 and 15 of BRAF gene revealed the T1796A (V599E) mutation in 32% of cases, and this alteration is significantly associated with PTC tall cell variant. Oncogenic rearrangements of RET and NTRK1 receptors were found in 33 and 5% of cases, respectively. No Ras mutations were detected. Overall, genetic alterations were detected in two-thirds of samples, and in no single case more than one mutational event was found simultaneously. Gene expression pro. ling of a subset of 31 tumors performed using cDNA microarray chips showed no strong differences in global gene expression among the different cases. However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement.