Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023, Lisboa, Portugal.
Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023, Lisboa, Portugal.
J Endocrinol Invest. 2019 Mar;42(3):313-318. doi: 10.1007/s40618-018-0919-8. Epub 2018 Jul 2.
The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. Our aim was to address whether EIF1AX mutations are present in the different stages of thyroid tumourigenesis (from hyperplasia to well-differentiated and to poorly differentiated/undifferentiated lesions), and to clarify its role in this process.
We analysed the EIF1AX gene in a series of 16 PDTC and ATC cases with coexistent well-differentiated regions and/or benign lesions. In EIF1AX mutant cases we also assessed the presence of RAS genes mutations.
We identified the mutation p.Ala113_splice in the EIF1AX gene in two PDTCs (neither present in the well-differentiated counterparts nor in the benign areas). One of these tumours also evidenced the mutation p.Glu61Arg in NRAS in both poorly and well-differentiated regions, further suggesting that the EIF1AX p.Ala113_splice mutation could be associated with tumoural progression. In another patient we did not find any EIF1AX alteration in the PDTC component, but we detected the EIF1AX p.Gly6_splice mutation in the PTC area (both regions were RAS wild-type). This mutation did not seem to be related with dedifferentiation.
According to our results, distinct mutations on EIF1AX may be related to different phenotypes/behaviours. Despite being a small series, which reflects the difficulty in retrieving PDTC and ATC surgical samples with well-differentiated and/or benign areas, our study may provide new insights into thyroid cancer tumourigenesis and dedifferentiation.
EIF1AX 基因最近被描述为一种新的甲状腺癌相关基因。其突变主要在低分化（PDTC）和间变性甲状腺癌（ATC）中报道，但也在高分化甲状腺癌（WDTC）和良性甲状腺病变中报道，尽管频率较低。我们的目的是探讨 EIF1AX 突变是否存在于甲状腺肿瘤发生的不同阶段（从增生到高分化和低分化/未分化病变），并阐明其在该过程中的作用。
我们分析了 16 例 PDTC 和 ATC 病例中 EIF1AX 基因的情况，这些病例中存在共存的高分化区域和/或良性病变。在 EIF1AX 突变病例中，我们还评估了 RAS 基因突变的存在。
我们在 2 例 PDTC 中发现了 EIF1AX 基因中的突变 p.Ala113_splice（在高分化对应物和良性区域均不存在）。其中一个肿瘤在低分化和高分化区域中也存在 NRAS 中的突变 p.Glu61Arg，进一步表明 EIF1AX p.Ala113_splice 突变可能与肿瘤进展有关。在另一名患者中，我们在 PDTC 成分中未发现任何 EIF1AX 改变，但在 PTC 区域检测到 EIF1AX p.Gly6_splice 突变（两个区域均为 RAS 野生型）。该突变似乎与去分化无关。
根据我们的结果，EIF1AX 上的不同突变可能与不同的表型/行为有关。尽管我们的研究系列较小，反映了在 PDTC 和 ATC 手术样本中难以获得高分化和/或良性区域，但它可能为甲状腺癌肿瘤发生和去分化提供新的见解。
