Molecular Oncology Group, Biodonostia Research Institute, San Sebastián, Gipuzkoa, Spain.
Department of Pathology, Donostia University Hospital, San Sebastián, Gipuzkoa, Spain.
Sci Rep. 2018 Apr 26;8(1):6613. doi: 10.1038/s41598-018-24780-7.
Early diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of dysplasia could greatly improve the outcome of affected patients. For the first time we compared the mutational landscape of non-progressing dysplasia (NPD; n = 42) with progressing dysplasia (PD; n = 24), along with patient-matched LSCC biopsies; a total of 90 samples. Using targeted next-generation sequencing identified non-synonymous mutations in six genes (PIK3CA, FGFR3, TP53, JAK3, MET, FBXW7), and mutations were validated by Sanger sequencing and/or qPCR. Analysis was extended in silico to 530 head and neck (HNSCC) cases using TCGA data. Mutations in PIK3CA and FGFR3 were detected in PD and LSCC cases, as well as other HNSCC cases, but absent in NPD cases. In contrast, mutations in JAK3, MET and FBXW7 were found in NPD cases but not PD, LSCC or other HNSCC cases. TP53 was the most frequently mutated gene in both PD and NPD cases. With the exception of R248W, mutations were mutually exclusive. Moreover, five of seven PD mutations were located in motif H2 of p53, whereas none of the NPD mutations were. In summary, we propose that the mutational profile of laryngeal dysplasia has utility for the early detection of patients at risk of progression.
早期诊断喉鳞状细胞癌（LSCC）在发育不良阶段可以大大改善患者的预后。我们首次比较了非进展性发育不良（NPD；n=42）与进展性发育不良（PD；n=24）的突变景观，以及患者匹配的 LSCC 活检；共 90 个样本。使用靶向下一代测序确定了六个基因（PIK3CA、FGFR3、TP53、JAK3、MET、FBXW7）中的非同义突变，并通过 Sanger 测序和/或 qPCR 进行了验证。分析通过 TCGA 数据扩展到 530 例头颈部（HNSCC）病例。PD 和 LSCC 病例以及其他 HNSCC 病例中检测到 PIK3CA 和 FGFR3 的突变，但在 NPD 病例中未检测到。相比之下，JAK3、MET 和 FBXW7 的突变在 NPD 病例中发现，但在 PD、LSCC 或其他 HNSCC 病例中未发现。TP53 是 PD 和 NPD 病例中最常突变的基因。除了 R248W 外，突变是相互排斥的。此外，PD 中的七个突变中有五个位于 p53 的 H2 基序中，而 NPD 中的突变都不在此基序中。总之，我们提出喉发育不良的突变谱可用于早期检测有进展风险的患者。
