Abstract：
The genetic repertoire of primary thyroid cancers (TCs) is well documented, but there is a considerable lack of molecular profiling in metastatic TCs. Here, we retrieved and analyzed the molecular and clinical features of 475 primary and metastatic TCs subjected to targeted DNA sequencing, from the cBioPortal database. The cohort included primary and metastatic samples from 276 papillary thyroid carcinomas (PTCs), 5 follicular thyroid carcinomas, 22 Hürthle cell carcinomas (HCCs), 127 poorly differentiated thyroid carcinomas (PDTCs), 30 anaplastic thyroid carcinomas (ATCs) and 15 medullary thyroid carcinomas. The ATCs had the highest tumor mutational burden and the HCCs the highest fraction of the genome altered. Compared to primary PTCs, the metastases had a significantly higher frequency of genetic alterations affecting TERT (51% vs 77%, P < 0.001), CDKN2A (2% vs 10%, P < 0.01), RET (2% vs 7%, P < 0.05), CDKN2B (1% vs 6%, P < 0.05) and BCOR (0% vs 4%, P < 0.05). The distant metastases had a significantly lower frequency of BRAF (64% vs 85%, P < 0.01) and a significantly higher frequency of NRAS (13% vs 3%, P < 0.05) hotspot mutations than the lymph node metastases. Metastases from HCCs and PDTCs were found to be enriched for NF1 (29%) and TP53 (18%) biallelic alterations, respectively. The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, P < 0.01) and PDTCs (43% vs 22%, P < 0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.
摘要：
原发性甲状腺癌（TCs）的遗传基因有很好的记录，但在转移性TC中相当缺乏分子谱分析。这里,我们检索并分析了475例进行靶向DNA测序的原发性和转移性TC的分子和临床特征，来自cBioPortal数据库。该队列包括来自276例甲状腺乳头状癌（PTC）的原发性和转移性样本，5个滤泡性甲状腺癌，22Hürthle细胞癌（HCC），127个低分化甲状腺癌（PDTC），30例间变性甲状腺癌（ATC）和15例髓样甲状腺癌。ATC具有最高的肿瘤突变负担，而HCC具有最高的基因组改变分数。与主要PTC相比，转移有更高的频率的遗传改变影响TERT（51％比77％，p7#60;0.001),CDKN2A（2%对10%，p#60;0.01),RET（2%对7%，p#60;0.05),CDKN2B（1%对6%，p#60；0.05)和BCOR(0%对4%，P#60；0.05）。远处转移的BRAF发生率明显较低（64%vs85%，p#60;0.01)和显著较高的NRAS频率(13%对3%，p#60；0.05)热点突变大于淋巴结转移。发现来自HCC和PDTC的转移酶富含NF1（29％）和TP53（18％）双等位基因改变，分别。ATCs的亚克隆突变频率显著高于PTCs（43%vs25%，p#60;0.01)和PDTC(43%对22%，P#60；0.01）。转移性TC富含临床信息性遗传改变，如RET易位，BRAF热点突变和NF1双等位基因丢失，可以在治疗上探索。
