Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.
Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.
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DOI：
10.1002/cncr.29038
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发表时间：
2014-12-01
期刊：
影响因子：
6.2
通讯作者：
Nikiforova MN
中科院分区：
文献类型：
--
作者：
Nikiforov YE;Carty SE;Chiosea SI;Coyne C;Duvvuri U;Ferris RL;Gooding WE;Hodak SP;LeBeau SO;Ohori NP;Seethala RR;Tublin ME;Yip L;Nikiforova MN
细针抽吸 (FNA) 细胞学检查是评估甲状腺结节的常用方法，尽管 20% 至 30% 的 FNA 细胞学检查结果不确定，这妨碍了对这些患者的适当治疗。滤泡性（或嗜酸细胞）肿瘤/可疑滤泡性（或嗜酸细胞）肿瘤 (FN/SFN) 是一种常见的不确定诊断，癌症风险约为 15% 至 30%。在这项研究中，作者测试了最完整的下一代测序 (NGS) 遗传标记组是否可以显着改善这些结节的癌症诊断。对来自手术结果已知的患者的 143 个连续 FNA 样本进行了细胞学诊断为 FN/SFN 的评估，其中包括 91 个回顾性样本和 52 个前瞻性样本。使用靶向 ThyroSeq v2 NGS 面板在专有测序仪上进行分析，该面板同时测试 13 个基因的点突变和甲状腺癌中发生的 42 种基因融合。 8 个基因的表达用于评估 FNA 样品的细胞组成。在整个队列中，组织学分析显示 104 个良性结节和 39 个恶性结节。最常见的点突变涉及神经母细胞瘤RAS病毒癌基因同源物（NRAS），其次是Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）、端粒酶逆转录酶（TERT）基因和促甲状腺激素受体（TSHR）基因。已确定的融合涉及甲状腺腺瘤相关（THADA）基因；过氧化物酶体增殖物激活受体 γ (PPARG) 基因；以及神经营养性酪氨酸激酶受体 3 型 (NTRK3) 基因。回顾性组和前瞻性组的表现特征相似。在所有 FN/SFN 结节中，术前 ThyroSeq v2 的敏感性为 90%（95% 置信区间 [CI]，80%-99%），特异性为 93%（95% CI，88%-98%），阳性预测值为 83%（95% CI，72%-95%），阴性预测值为 96%（95% CI， 92%-100%）和 92% 准确度（95% CI，88%-97%）。目前的结果表明，使用广泛的 NGS 组合对甲状腺结节进行全面的基因分型可以通过 FN/SFN 细胞学对结节进行高度准确的诊断，并应有助于对这些患者进行最佳管理。
Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor γ (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.
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影响因子：
--
作者：
Kloth L;Belge G;Burchardt K;Loeschke S;Wosniok W;Fu X;Nimzyk R;Mohamed SA;Drieschner N;Rippe V;Bullerdiek J
通讯作者：
Bullerdiek J
影响因子：
3.4
作者：
Yassa, Leila;Cibas, Edmund S.;Alexander, Erik K.
通讯作者：
Alexander, Erik K.
DOI：
10.1073/pnas.1321937111
发表时间：
2014-03-18
影响因子：
11.1
作者：
Kelly, Lindsey M.;Barila, Guillermo;Nikiforov, Yuri E.
通讯作者：
Nikiforov, Yuri E.
影响因子：
5.8
作者：
Nikiforov, Yuri E.;Steward, David L.;Nikiforova, Marina N.
通讯作者：
Nikiforova, Marina N.
影响因子：
1.3
作者：
Baloch, Zubair W.;LiVolsi, Virginia A.;Frable, William J.
通讯作者：
Frable, William J.