The genomic landscape of papillary thyroid carcinoma on next-generation sequencing in patients undergoing total thyroidectomy.

IF 2.3 3区医学 Q2 SURGERY

World Journal of Surgery Pub Date : 2024-11-05 DOI:10.1002/wjs.12389

Karunakaran Poongkodi, Sumathi Periyasamy, Raj Ashok Gurunathan, Vijayakumar Krishnasamy, Deepak Jayakumar, Ramesh Subburaman, Sujatha Jayaraman, Sudheesh K Prabhudas

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Abstract

Background: Thyroidectomy is increasingly performed for suspected malignancy. This cohort study aimed to identify genetic markers associated with malignancy and determine the molecular landscape of papillary thyroid carcinoma (PTC) through next-generation sequencing (NGS) in patients undergoing total thyroidectomy.

Patients and methods: Among 116 surgical candidates, 103 patients (age = 42.9 ± 13.7 years; Male: Female = 14:89) with benign or malignant thyroid nodules were eligible. Live thyroid tissue samples harvested intraoperatively with adequate DNA and RNA yield were subjected to NGS on the Illumina NovaSeq 6000 platform for genomic and transcriptomic analysis, respectively.

Results: Histopathology comprised 20 malignant (19.4%) and 83 benign (80.6%) cases, including 16 PTC (15.5%) cases. On NGS, single nucleotide polymorphisms (SNPs) in NTRK1 at NC_000001.11:156879016 on chromosome 1 and ALK at NC_000002.12:29717663 on chromosome 2 were frequent in malignant lesions (p < 0.05). A SNP in ALK at NC_000002.12:29193706 was consistently a homozygous alternate allele across the cohort. DNA-sequencing of PTC lesions identified recurrent somatic mutations in BRAF (100%), ALK (56.3%), RET (18.8%), PIK3CA (12.5%), NTRK1 (12.5%), NTRK2 (87.5%), NTRK3 (12.5%), NRAS (6.3%), and PTCH1 (31.3%) genes. RNA sequencing revealed novel fusion genes, including MKRN1-BRAF, RN7SL1-CDH1, IRF2BPL-MED12, MED12-IRF2BPL, CPM-MDM2, and AC005895.3-PDGFRB. In receiver operative characteristics analysis, the AUCs of ALK mutation predicting recurrence and metastases were 0.818 and 0.783.

Conclusion: This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.

Trial registration no: CTRI/2020/09/027607 dt 04/09/2020; REF/2020/08/036119.

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甲状腺全切除术患者的新一代测序甲状腺乳头状癌基因组图谱。

背景：甲状腺切除术越来越多地用于疑似恶性肿瘤。这项队列研究旨在通过下一代测序（NGS），在接受甲状腺全切除术的患者中鉴定与恶性肿瘤相关的遗传标记物，并确定甲状腺乳头状癌（PTC）的分子结构：在 116 名手术候选人中，103 名患有良性或恶性甲状腺结节的患者（年龄 = 42.9 ± 13.7 岁；男女比例 = 14:89）符合条件。术中采集的活体甲状腺组织样本具有足够的 DNA 和 RNA 产量，分别在 Illumina NovaSeq 6000 平台上进行 NGS 基因组和转录组分析：组织病理学结果显示，有 20 例恶性肿瘤（19.4%）和 83 例良性肿瘤（80.6%），其中包括 16 例 PTC（15.5%）。在 NGS 中，位于 1 号染色体 NC_000001.11:156879016 的 NTRK1 和位于 2 号染色体 NC_000002.12:29717663 的 ALK 的单核苷酸多态性（SNPs）在恶性病变中很常见（p 结论：这项印度研究发现了新型体细胞突变：这项印度研究发现了 PTC 中的新型体细胞突变和融合基因，揭示了一种独特的基因组格局，对精准诊断和个性化治疗具有重要意义。术中活体取样的 NGS 技术有望用于晚期/转移性 PTC 病例的预后判断和治疗优化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Surgery 医学-外科

CiteScore

5.10

自引率

3.80%

发文量

460

审稿时长

3 months

期刊介绍： World Journal of Surgery is the official publication of the International Society of Surgery/Societe Internationale de Chirurgie (iss-sic.com). Under the editorship of Dr. Julie Ann Sosa, World Journal of Surgery provides an in-depth, international forum for the most authoritative information on major clinical problems in the fields of clinical and experimental surgery, surgical education, and socioeconomic aspects of surgical care. Contributions are reviewed and selected by a group of distinguished surgeons from across the world who make up the Editorial Board.