Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma IdentifiesRASandPIK3CAMutations as Negative Survival Predictors

doi:10.3390/cancers12071973

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標題:	Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma IdentifiesRASandPIK3CAMutations as Negative Survival Predictors
作者:	Lai, Wei-An Liu, Chih-Yi Lin, Shih-Yao Chen, Chien-Chin Hang, Jen-Fan
貢獻者:	Taipei Vet Gen Hosp, Dept Pathol & Lab Med Sijhih Cathay Gen Hosp, Div Pathol Far Eastern Mem Hosp, Dept Pathol Ditmanson Med Fdn Chia Yi Christian Hosp, Dept Pathol Chia Nan Univ Pharm & Sci, Dept Cosmet Sci Natl Yang Ming Univ, Sch Med
關鍵字:	anaplastic thyroid carcinoma RAS BRAF(V600E) PIK3CA TERTpromoter TP53
日期:	2020
上傳時間:	2022-11-18 11:23:52 (UTC+8)
出版者:	Mdpi
摘要:	Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, includingBRAF,RAS,PIK3CA,TERTpromoter,TP53,POLE, and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry.BRAF(V600E)andRASmutations were identified in 25.9% and 40.7% of ATC, respectively.BRAF(V600E)mutation was significantly associated with coexisting papillary thyroid carcinoma (p= 0.009) andRASmutations with female gender (p= 0.012). In univariant analysis, the non-BRAF/RAStumors were significantly associated with the presence of a sarcomatoid pattern (p= 0.045).PIK3CA,TERTpromoter, andTP53mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D orPOLEmutations were detected. In survival analyses,RASandPIK3CAmutations were significantly associated with inferior outcomes (p= 0.03 andp= 0.006, respectively). In conclusion, driver mutations in ATC are associated with distinct clinicopathological features.RASandPIK3CAmutations were negative predictors for patient survival. Emerging therapeutic agents targeting BRAF, RAS, and PI3 kinase may benefit a substantial proportion of ATC patients.
關聯:	Cancers, v.12, n.7, pp.13
显示于类别:	[化妝品應用與管理系(所)] 期刊論文

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