RESUMO
Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
Assuntos
Acidente Nuclear de Chernobyl , Radioisótopos do Iodo , Metástase Linfática , Mutação , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Metástase Linfática/genética , Masculino , Adulto , Feminino , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Adolescente , Proteínas Proto-Oncogênicas B-raf/genética , Adulto Jovem , Linfonodos/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Criança , Genômica , Pessoa de Meia-Idade , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/patologia , Pescoço/patologia , Regulação Neoplásica da Expressão GênicaRESUMO
Single nucleus RNA-sequencing is critical in deciphering tissue heterogeneity and identifying rare populations. However, current high throughput techniques are not optimized for rare target populations and require tradeoffs in design due to feasibility. We provide a novel snRNA pipeline, MulipleXed Population Selection and Enrichment snRNA-sequencing (XPoSE-seq), to enable targeted snRNA-seq experiments and in-depth transcriptomic characterization of rare target populations while retaining individual sample identity.