Bim Larissa Valdemarin, Carneiro Thaise Nayane Ribeiro, Buzatto Vanessa Candiotti, Colozza-Gama Gabriel Avelar, Koyama Fernanda C, Thomaz Debora Mota Dias, de Jesus Paniza Ana Carolina, Lee Eunjung Alice, Galante Pedro Alexandre Favoretto, Cerutti Janete Maria
Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 Andar, São Paulo 04039-032, SP, Brazil.
Centro de Oncologia Molecular, Hospital Sírio-Libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo 01308-060, SP, Brazil.
Cancers (Basel). 2021 Oct 15;13(20):5184. doi: 10.3390/cancers13205184.
Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20-30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (, and ) and fusions were described. and variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, , or positive samples. Negative samples were separated in two clusters, following the expression pattern of the or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology.
甲状腺癌是最常见的内分泌恶性肿瘤。然而，滤泡状甲状腺癌（FTC）、许特莱细胞癌（HCC）和甲状腺乳头状癌滤泡变体（FVPTC）及其良性对应物的细胞学诊断对术前诊断来说是一项挑战。近20%-30%的甲状腺活检结节被归类为具有不确定的恶性风险，这给医疗保健系统带来了成本。基于此，对120例患者进行了先前在甲状腺癌中描述的主要驱动基因突变筛查。随后，对作为诊断错误主要来源的14例突变阴性病例（FTC、HCC或FVPTC）进行了RNA测序分析。描述了候选驱动基因（、和）中的体细胞变异和融合情况。和变异进行了验证。此外，将驱动基因阴性样本的表达谱与16例BRAF V600E、或阳性样本进行了比较。阴性样本根据或BRAF V600E阳性样本的表达模式分为两个簇。两个阴性组均显示出不同的BRS、ERK和TDS评分、肿瘤突变负担、信号通路和免疫细胞谱。总之，我们在此报告了新的基因变异，并描述了可能影响术前诊断的癌症相关途径，为甲状腺肿瘤生物学提供了见解。
