Pathology Unit 2, Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Integrated Biology of Rare Tumors, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Front Endocrinol (Lausanne). 2023 Oct 5;14:1267499. doi: 10.3389/fendo.2023.1267499. eCollection 2023.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of follicular cell-derived TCs, and V600E, mutations, and gene fusions are well-established drivers. mutations were described in specific sets of TC patients but represent a rare event in adult TC patients.
Here, we report the molecular characterization of 30 retrospective follicular cell-derived thyroid tumors, comprising PTCs (90%) and poorly differentiated TCs (10%), collected at our Institute. We performed DNA whole-exome sequencing using patient-matched control for somatic mutation calling, and targeted RNA-seq for gene fusion detection. Transcriptional profiles established in the same cohort by microarray were investigated using three signaling-related gene signatures derived from The Cancer Genome Atlas (TCGA).
The occurrence of V600E (44%), mutations (13%), and gene fusions (13%) was confirmed in our cohort. In addition, in two patients lacking known drivers, mutations of the gene (p.D1709N and p.D1810V) were identified. mutations occur in two adult patients with follicular-pattern lesions, and in one of them a second concurrent mutation (p.R459*) is also observed. Additional putative drivers include gene (p.P2130A mutation), identified in a patient with a rare solid-trabecular subtype of PTC. Transcriptomics indicates that tumors are RAS-like, whereas the -mutated tumor displays a borderline RAS-/BRAF-like subtype. We also provide an overview of and mutations in thyroid lesions by investigating the COSMIC database.
Even though small, our series recapitulates the genetic background of PTC. Furthermore, we identified mutations, one of which is previously unreported in thyroid lesions. For these less common alterations and for patients with unknown drivers, we provide signaling information applying TCGA-derived classification.
甲状腺癌（TC）中最常见的类型是甲状腺乳头状癌（PTC）。几项基因组和转录组研究探索了滤泡细胞衍生 TCs 的分子图谱，V600E 突变、突变和基因融合是公认的驱动因素。在特定的 TC 患者群体中描述了 突变，但在成人 TC 患者中是罕见事件。
在这里，我们报告了我们研究所收集的 30 例回顾性滤泡细胞衍生甲状腺肿瘤的分子特征，包括 PTC（90%）和低分化 TC（10%）。我们使用患者匹配对照进行全外显子组 DNA 测序以进行体细胞突变调用，并进行靶向 RNA-seq 以检测基因融合。通过微阵列在同一队列中建立的转录谱使用来自癌症基因组图谱（TCGA）的三个信号相关基因特征进行了研究。
在我们的队列中证实了 V600E（44%）、突变（13%）和基因融合（13%）的发生。此外，在两名缺乏已知驱动因素的患者中，鉴定出基因的突变（p.D1709N 和 p.D1810V）。在两名患有滤泡样病变的成年患者中发生了 突变，其中一名患者还观察到第二种同时存在的突变（p.R459*）。其他潜在的驱动因素包括患者罕见的实性小梁型 PTC 中发现的基因（p.P2130A 突变）。转录组学表明 肿瘤呈 RAS 样，而 -突变肿瘤显示出边界 RAS-/BRAF 样亚型。通过调查 COSMIC 数据库，我们还提供了甲状腺病变中 突变和 突变的概述。
尽管很小，但我们的系列概括了 PTC 的遗传背景。此外，我们鉴定了 突变，其中一种在甲状腺病变中以前没有报道过。对于这些不太常见的改变和未知驱动因素的患者，我们应用 TCGA 衍生的分类提供了信号信息。
