Mutation profiles of follicular thyroid tumors by targeted sequencing
Abstract Background One of the major challenges remaining in the classification of thyroid tumor is the determination of whether a nodule is benign or malignant. We aimed to characterize the mutational profiles of follicular thyroid tumor and to identify markers with potential diagnostic and prognos...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13000-019-0817-1 |
| _version_ | 1818151397267341312 |
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| author | Huanli Duan Xiaoding Liu Xinyu Ren Hui Zhang Huanwen Wu Zhiyong Liang |
| author_facet | Huanli Duan Xiaoding Liu Xinyu Ren Hui Zhang Huanwen Wu Zhiyong Liang |
| author_sort | Huanli Duan |
| collection | DOAJ |
| description | Abstract Background One of the major challenges remaining in the classification of thyroid tumor is the determination of whether a nodule is benign or malignant. We aimed to characterize the mutational profiles of follicular thyroid tumor and to identify markers with potential diagnostic and prognostic implications. Methods Targeted sequencing with a panel of 18 thyroid cancer-related genes was performed on 48 tissue samples from follicular thyroid adenoma (FTA), 32 follicular tumors of uncertain malignant potential (FT-UMP), 17 well-differentiated tumors of uncertain malignant potential (WDT-UMP) and 53 samples from follicular thyroid carcinoma (FTC). The correlation of mutation profiles and clinicopathological features and prognosis were also analyzed. Results We identified 95 nonsilent mutations spanning 14 genes. Specifically, TERT promoter (TERTp) mutations were exclusively detected in FTC. A total of 80% EIF1AX exon 2 mutations (4/5) and 75% TSHR mutations (3/4) occurred in FTA, whereas the rest of them occurred in FT-UMP. KRAS mutations and TP53 mutations were only presented in borderline or malignant tumors. H/N-RAS mutations were detected in all four subtypes, but were most commonly found in WDT-UMP (p = 0.031). All N-RAS mutations were located at codon 61. BRAF V600E and RET fusion were absent in the entire cohort. In FTC cases, EIF1AX mutations were all located at intron 5/exon 6 and correlated with advanced disease (p = 0.032). Both EIF1AX and TERTp mutations predicted shorter disease-free survival (p = 0.007, p = 0.024, respectively). Further analysis revealed that TERTp mutations were correlated with shorter disease-free survival in patients with minimally invasive /encapsulated angioinvasive FTC (p = 0.017), but not in those with widely invasive FTC (p = 0.297). Conclusion TERTp, EIF1AX, TSHR, H/N/K-RAS and TP53 mutations may have diagnostic or prognostic potential in follicular thyroid tumors. TERTp mutations may predict a poor outcome in patients with minimally invasive/encapsulated angioinvasive FTC. |
| first_indexed | 2024-12-11T13:38:10Z |
| format | Article |
| id | doaj.art-a968499599e9419ea70ba41d07d1a6f9 |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-12-11T13:38:10Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-a968499599e9419ea70ba41d07d1a6f92022-12-22T01:04:56ZengBMCDiagnostic Pathology1746-15962019-05-0114111010.1186/s13000-019-0817-1Mutation profiles of follicular thyroid tumors by targeted sequencingHuanli Duan0Xiaoding Liu1Xinyu Ren2Hui Zhang3Huanwen Wu4Zhiyong Liang5Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical CollegeMolecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical CollegeMolecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical CollegeMolecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical CollegeMolecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical CollegeMolecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical CollegeAbstract Background One of the major challenges remaining in the classification of thyroid tumor is the determination of whether a nodule is benign or malignant. We aimed to characterize the mutational profiles of follicular thyroid tumor and to identify markers with potential diagnostic and prognostic implications. Methods Targeted sequencing with a panel of 18 thyroid cancer-related genes was performed on 48 tissue samples from follicular thyroid adenoma (FTA), 32 follicular tumors of uncertain malignant potential (FT-UMP), 17 well-differentiated tumors of uncertain malignant potential (WDT-UMP) and 53 samples from follicular thyroid carcinoma (FTC). The correlation of mutation profiles and clinicopathological features and prognosis were also analyzed. Results We identified 95 nonsilent mutations spanning 14 genes. Specifically, TERT promoter (TERTp) mutations were exclusively detected in FTC. A total of 80% EIF1AX exon 2 mutations (4/5) and 75% TSHR mutations (3/4) occurred in FTA, whereas the rest of them occurred in FT-UMP. KRAS mutations and TP53 mutations were only presented in borderline or malignant tumors. H/N-RAS mutations were detected in all four subtypes, but were most commonly found in WDT-UMP (p = 0.031). All N-RAS mutations were located at codon 61. BRAF V600E and RET fusion were absent in the entire cohort. In FTC cases, EIF1AX mutations were all located at intron 5/exon 6 and correlated with advanced disease (p = 0.032). Both EIF1AX and TERTp mutations predicted shorter disease-free survival (p = 0.007, p = 0.024, respectively). Further analysis revealed that TERTp mutations were correlated with shorter disease-free survival in patients with minimally invasive /encapsulated angioinvasive FTC (p = 0.017), but not in those with widely invasive FTC (p = 0.297). Conclusion TERTp, EIF1AX, TSHR, H/N/K-RAS and TP53 mutations may have diagnostic or prognostic potential in follicular thyroid tumors. TERTp mutations may predict a poor outcome in patients with minimally invasive/encapsulated angioinvasive FTC.http://link.springer.com/article/10.1186/s13000-019-0817-1Follicular thyroid tumorTargeted next generation sequencingTERT promoter mutation |
| spellingShingle | Huanli Duan Xiaoding Liu Xinyu Ren Hui Zhang Huanwen Wu Zhiyong Liang Mutation profiles of follicular thyroid tumors by targeted sequencing Diagnostic Pathology Follicular thyroid tumor Targeted next generation sequencing TERT promoter mutation |
| title | Mutation profiles of follicular thyroid tumors by targeted sequencing |
| title_full | Mutation profiles of follicular thyroid tumors by targeted sequencing |
| title_fullStr | Mutation profiles of follicular thyroid tumors by targeted sequencing |
| title_full_unstemmed | Mutation profiles of follicular thyroid tumors by targeted sequencing |
| title_short | Mutation profiles of follicular thyroid tumors by targeted sequencing |
| title_sort | mutation profiles of follicular thyroid tumors by targeted sequencing |
| topic | Follicular thyroid tumor Targeted next generation sequencing TERT promoter mutation |
| url | http://link.springer.com/article/10.1186/s13000-019-0817-1 |
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