Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis.
Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis.
复制标题
传统甲状腺乳头状癌脑转移的纵向基因组进化
DOI：
10.3389/fonc.2021.620924
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发表时间：
2021
影响因子：
4.7
通讯作者：
Shu Y
中科院分区：
文献类型：
--
作者：
Luo H;Liao X;Qin Y;Hou Q;Xue Z;Liu Y;Shen F;Wang Y;Jiang Y;Song L;Chen H;Zhang L;Wei T;Dai L;Yang L;Zhang W;Li Z;Xu H;Zhu J;Shu Y
脑转移在甲状腺乳头状癌（PTC）中极为罕见，但预示着不良预后。很少对逐步转移的病灶进行动态评估以确定PTC脑转移的纵向基因组演变。
对按时间顺序切除的标本进行了全外显子组测序分析，包括四个转移淋巴结（lyn 1 - 4）和脑转移病灶（BM）。重建系统发育树以推断转移模式和潜在的功能性突变。
与lyn1相比，具有TSC2双等位基因突变的同侧转移病灶（lyn2 - 4和BM）表明其与多灶性肿瘤有不同的遗传起源。Lyn 3/4，尤其是lyn4与BM表现出高度的遗传相似性。除了相似的突变组成和特征外，在lyn3/4和BM中还观察到共享的功能性突变（CDK4R24C，TP53R342*）。这些突变的频率随着转移进展逐渐增加。一致地，在PTC细胞中敲除TP53并引入CDK4R24C显著降低了放射性碘摄取并增加了转移能力。
肿瘤演变过程中CDK4和TP53的基因突变可能有助于PTC的淋巴结和脑转移。
Brain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC. Chronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations. Contrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability. Genomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.
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影响因子：
64.5
作者：
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通讯作者：
Cancer Genome Atlas Research Network
影响因子：
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作者：
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通讯作者：
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影响因子：
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