Division of Endocrinology, Diabetes, Metabolism, & Nutrition, Mayo Clinic, Rochester, Minnesota.
Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
J Clin Endocrinol Metab. 2020 Jul 1;105(7):e2346-57. doi: 10.1210/clinem/dgaa246.
Clinical applications of genomic assessment of thyroid cancers are rapidly evolving.
OBJECTIVES, DESIGN, AND SETTING: We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable.
Progressive and metastatic, and/or rare, thyroid cancers were studied, 2012 to 2016, at Mayo Clinic sites.
The intervention was Foundation One tumor interrogation.
Main outcome measures included genomic alterations, patient characteristics, and overall survival.
Samples from 55 patients were evaluated: 20 anaplastic thyroid cancers (ATCs) (36%), 25 radioactive iodine-refractory differentiated thyroid cancers (DTCs)/poorly differentiated thyroid cancers (PDTCs) (45%; 14 papillary thyroid cancer [PTCs], 6 PDTCs, 5 Hürthle cell cancers), 8 medullary thyroid cancers (MTCs) (15%), and 2 others (a spindle epithelial tumor with thymus-like differentiation, and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs, and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs)-but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTCs/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, and 25% HRAS mutations. Of patient tumors with nonmutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations. Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC.
Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.
甲状腺癌的基因组评估的临床应用正在迅速发展。
目的、设计和环境：我们研究了具有威胁性和罕见甲状腺癌的患者的肿瘤样本，以确定可能与结果相关或具有治疗潜力的基因组改变。
2012 年至 2016 年，在梅奥诊所的多个站点对进行性和转移性、或罕见的甲状腺癌患者进行了研究。
干预措施是 FoundationOne 肿瘤检测。
主要观察指标包括基因组改变、患者特征和总生存率。
共评估了 55 例患者的样本：20 例间变性甲状腺癌（ATC）（36%），25 例放射性碘难治性分化型甲状腺癌（DTC）/低分化甲状腺癌（PDTC）（45%；14 例乳头状甲状腺癌[PTC]、6 例 PDTC、5 例 Hurthle 细胞癌）、8 例髓样甲状腺癌（MTC）（15%）和 2 例其他肿瘤（具有胸腺样分化的梭形上皮肿瘤和原发性甲状腺肉瘤）。总的来说，72%的 DTC、79%的 ATC 和 75%的 MTC 被认为具有潜在的可治疗性改变。最常见的突变是 TERT 启动子（56%的 DTC、68%的 ATC）-但目前无法靶向治疗。40%的 DTC/PDTC（83%的 PTC）和 32%的 ATC 发现可靶向的 BRAFV600E 突变；75%的 MTC 存在可靶向的 RET 突变，25%的 HRAS 突变。在非 BRAFV600E 突变的患者肿瘤中，53%的 DTC/PDTC 和 69%的 ATC 有其他潜在的可治疗性突变。我们系列研究中预后不良的转移性 DTC/PDTC 的基因组改变也与 ATC 非常相似。
虽然对预后良好的甲状腺癌进行基因组检测似乎并不明智，但在需要全身治疗的转移性甲状腺癌患者的大多数肿瘤中，均显示出具有潜在治疗潜力的突变，这表明选择性应用该技术具有合理性。
