Colli Sandra Lorena, Boycho Marisa Esther, Papendieck Patricia, Mangone Franco Mauricio, Chiesa Ana, García Lombardi Mercedes, Medín Martín, De Matteo Elena Noemí, Lorenzetti Mario Alejandro, Preciado María Victoria
División Patología, Hospital de Niños "Dr. Ricardo Gutiérrez", Buenos Aires, Argentina.
Laboratorio de Biología Molecular, División Patología, Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, Hospital de Niños "Dr. Ricardo Gutiérrez", Buenos Aires, Argentina.
PLoS One. 2025 May 8;20(5):e0323271. doi: 10.1371/journal.pone.0323271. eCollection 2025.
Thyroid cancer is the primary endocrine malignancy, exhibiting distinct genomic drivers. The frequency of genetic alterations varies between adult and pediatric groups and across geographic regions and ethnicities. Molecular markers may serve as prognostic tools and/or specific treatment-selection tools in papillary thyroid carcinoma (PTC) in children. We sought to characterize molecular alterations in pediatric PTC from Argentina and test a future laboratory algorithm for molecular diagnosis and stratification. Immunohistochemistry, fluorescence in situ hybridization, and Sanger sequencing were performed on 57 pediatric PTC samples. This study assesses multiple genetic alterations, including fusions in RET, ALK, MET, BRAF, and NTRK genes, as well as the BRAF V600E single nucleotide variant. Fusions in known oncogenes were observed in 29.8% of cases (6 in RET, 5 in ALK, 4 in NTRK3, 1 in BRAF, and 1 in MET). The BRAF V600E SNV was detected in 12.3% of cases. Larger tumor size and higher initial risk were associated with genetic alterations (P = 0.027 and P = 0. 036, respectively). Designing a laboratory algorithm following an increasing order of complexity provided a reliable molecular testing platform that reduces the requirement for NGS screening. These results also broaden the data on PTC alterations in children from Argentina.
甲状腺癌是主要的内分泌恶性肿瘤，具有独特的基因组驱动因素。基因改变的频率在成人和儿童群体之间以及不同地理区域和种族之间有所不同。分子标志物可作为儿童甲状腺乳头状癌（PTC）的预后工具和/或特定的治疗选择工具。我们试图对来自阿根廷的儿童PTC中的分子改变进行特征描述，并测试一种未来用于分子诊断和分层的实验室算法。对57例儿童PTC样本进行了免疫组织化学、荧光原位杂交和桑格测序。本研究评估了多种基因改变，包括RET、ALK、MET、BRAF和NTRK基因的融合，以及BRAF V600E单核苷酸变异。在29.8%的病例中观察到已知致癌基因的融合（RET中有6例，ALK中有5例，NTRK3中有4例，BRAF中有1例，MET中有1例）。在12.3%的病例中检测到BRAF V600E单核苷酸变异。肿瘤较大和初始风险较高与基因改变相关（分别为P = 0.027和P = 0.036）。按照复杂性递增顺序设计实验室算法提供了一个可靠的分子检测平台，减少了对二代测序筛查的需求。这些结果也拓宽了关于阿根廷儿童PTC改变的数据。
