Cancer-related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings
Cancer-related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings
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DOI：
10.1111/hepr.13529
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发表时间：
2020-06-30
影响因子：
4.2
通讯作者：
Enomoto, Nobuyuki
中科院分区：
文献类型：
--
作者：
Muraoka, Masaru;Maekawa, Shinya;Enomoto, Nobuyuki
目的通过新一代基因测序技术的研究，肝细胞癌（HCC）中与癌症相关的遗传畸变现象逐渐清晰。然而，目前尚不清楚遗传畸变与影像学和组织学结果的关系。方法对117例经福尔马林固定的原发性肝肿瘤石蜡包埋标本进行50个肿瘤相关基因的下一代测序和hTERT的数字聚合酶链反应。通过钆塞酸增强磁共振成像、对比增强计算机断层扫描、对比增强超声和弥散加权成像磁共振成像的信息，将肿瘤分为几个成像组，然后研究遗传畸变与成像和组织学之间的相关性。结果突变频率最高的是TERT（61.5%），其次是TP 53（42.7%）、RB 1（24.8%）和CTNNB 1（18.8%）。肝肿瘤分为6种影像学类型/分级，hTERT突变的发生率随影像学/组织学分级的增高而增高（P分别为0.026和0.13），而TP 53突变的发生率无明显增高趋势（P分别为0.78和1.00）。关注每个肿瘤中的突变，尽管hTERT的变异频率（VF）没有改变（分别为P = 0.36和0.14）与影像学/组织学分级相关，但TP 53 VF显著增加（P = 0.004和= 50%（危害比，3.79;P = 0.020））被提取为原发性HCC患者复发的独立风险。结论hTERT突变和TP 53突变VF的发生率增加是HCC进展的特征性特征，可通过影像学/组织学检查进行诊断。
Aim The landscape of cancer-related genetic aberrations in hepatocellular carcinoma (HCC) has gradually become clear through recent next-generation sequencing studies. However, it remains unclear how genetic aberrations correlate with imaging and histological findings. Methods Using 117 formalin-fixed paraffin-embedded specimens of primary liver tumors, we undertook targeted next-generation sequencing of 50 cancer-related genes and digital polymerase chain reaction ofhTERT. After classifying tumors into several imaging groups by hierarchal clustering with the information from gadoxetic acid enhanced magnetic resonance imaging, contrast-enhanced computed tomography, contrast-enhanced ultrasound, and diffusion-weighted imaging magnetic resonance imaging, the correlation between genetic aberrations and imaging and histology were investigated. Results Most frequent mutations werehTERT(61.5%), followed byTP53(42.7%),RB1(24.8%), andCTNNB1(18.8%). Liver tumors were classified into six imaging groups/grades, and the prevalence ofhTERTmutations tended to increase with the advancement of imaging/histological grades (P = 0.026 and 0.13, respectively), whereas no such tendency was evident forTP53mutation (P = 0.78 and 1.00, respectively). Focusing on the mutations in each tumor, although the variant frequency (VF) ofhTERTdid not change (P = 0.36 and 0.14, respectively) in association with imaging/histological grades,TP53VF increased significantly (P = 0.004 and = 50% (hazard ratio, 3.79;P = 0.020) was extracted as an independent risk for recurrence in primary HCC patients. Conclusions Increased prevalence ofhTERTmutation and increasedTP53mutation VF are characteristic features of HCC progression, diagnosed with imaging/histological studies.