Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
J Clin Endocrinol Metab. 2023 Dec 21;109(1):143-150. doi: 10.1210/clinem/dgad458.
Fusion oncogenes, especially those involving RET or NTRK, are known drivers of papillary thyroid cancer (PTC). They are prevalent in pediatric patients and correlate with aggressive tumor behavior.
We explored the age dependence of fusion oncogenes and aggressive tumor behavior in young adult PTC patients.
We examined 150 tumors from 142 PTC patients aged between 17∼35 years old with established tumor-node-metastasis stages. Oncogenic drivers and the thyroid differentiation score (TDS) were determined by DNA and RNA sequencing of a target panel. Transcriptome analysis was performed in PTCs with RET fusions.
Among 150 PTCs, we detected BRAF V600E (n = 105), RET fusions (n = 15), NTRK3 fusions (n = 8), and BRAF fusions (n = 4). We found that fusion oncogenes were associated with nodal metastasis when age was tiered into 3 groups: <25 years, 25∼29 years, and 30∼35 years. Patients under 25 years old showed a marginal increase in tumor stage compared to those over 25 years (75.00% vs 21.74%, P = .0646). Risk of lateral lymph node metastasis increased with younger age (75.00% vs 27.27% vs 8.33%, P = .0369). As with advanced tumor and node stage, patients harboring fusion oncogenes and aged under 25 years showed the lowest TDS; genes associated with immunoglobulin production and production of molecular mediators of the immune response were significantly upregulated.
Adult PTC patients under 25 years with fusion oncogenes showed a tendency toward advanced tumor stage and lower thyroid differentiation. Integrating onset age together with oncogenic alterations is worthwhile when managing adult PTC patients.
融合癌基因，特别是涉及 RET 或 NTRK 的融合癌基因，是甲状腺乳头状癌（PTC）的已知驱动基因。它们在儿科患者中较为常见，与侵袭性肿瘤行为相关。
我们探讨了年轻成年 PTC 患者中融合癌基因与侵袭性肿瘤行为的年龄依赖性。
我们检测了 142 例年龄在 17∼35 岁之间的 PTC 患者的 150 个肿瘤，这些患者的肿瘤分期、淋巴结转移分期和远处转移分期已确定。通过目标面板的 DNA 和 RNA 测序确定致癌驱动因素和甲状腺分化评分（TDS）。对具有 RET 融合的 PTC 进行转录组分析。
在 150 例 PTC 中，我们检测到 BRAF V600E（n = 105）、RET 融合（n = 15）、NTRK3 融合（n = 8）和 BRAF 融合（n = 4）。我们发现，当年龄分为 3 组（<25 岁、25∼29 岁和 30∼35 岁）时，融合癌基因与淋巴结转移相关。与 25 岁以上的患者相比，25 岁以下的患者肿瘤分期略有增加（75.00%比 21.74%，P =.0646）。侧方淋巴结转移的风险随年龄的降低而增加（75.00%比 27.27%比 8.33%，P =.0369）。与晚期肿瘤和淋巴结分期一样，携带融合癌基因且年龄小于 25 岁的患者 TDS 最低；与免疫球蛋白产生和免疫反应分子介质产生相关的基因显著上调。
25 岁以下携带融合癌基因的成年 PTC 患者表现出肿瘤分期较高和甲状腺分化较低的趋势。在管理成年 PTC 患者时，将发病年龄与致癌改变相结合是值得的。
