Risk stratification by combining common genetic mutations and TERT promoter methylation in papillary thyroid cancer
Purpose Risk stratification based on somatic mutations in TERT promoter and BRAF / RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This stu...
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| Published in | Endocrine Vol. 85; no. 1; pp. 304 - 312 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Springer US
01.07.2024
Springer Nature B.V |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Purpose
Risk stratification based on somatic mutations in
TERT
promoter and
BRAF
/
RAS
has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that
TERT
promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of
BRAF
/
RAS
mutations,
TERT
promoter mutations, and
TERT
promoter methylation in PTC.
Methods
The relationships of
BRAF
/
RAS
mutations,
TERT
promoter mutations, and
TERT
promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC.
Results
TERT
promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with
BRAF
/
RAS
mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of
BRAF
/
RAS
and
TERT
alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both
BRAF
/
RAS
and
TERT
alterations had higher rates of tumor recurrence (13.6% vs 1.5%,
P
= 0.042) and disease progression (24.4% vs 3.3%,
P
< 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of
BRAF
/
RAS
and
TERT
alterations, but not
BRAF
/
RAS
or
TERT
alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79–59.81,
P
= 0.009).
Conclusions
This study suggested that comprehensively analysis of
BRAF
/
RAS
mutations,
TERT
promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC. |
|---|---|
| AbstractList | Risk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation in PTC.PURPOSERisk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation in PTC.The relationships of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC.METHODSThe relationships of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC.TERT promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with BRAF/RAS mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of BRAF/RAS and TERT alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both BRAF/RAS and TERT alterations had higher rates of tumor recurrence (13.6% vs 1.5%, P = 0.042) and disease progression (24.4% vs 3.3%, P < 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of BRAF/RAS and TERT alterations, but not BRAF/RAS or TERT alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79-59.81, P = 0.009).RESULTSTERT promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with BRAF/RAS mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of BRAF/RAS and TERT alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both BRAF/RAS and TERT alterations had higher rates of tumor recurrence (13.6% vs 1.5%, P = 0.042) and disease progression (24.4% vs 3.3%, P < 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of BRAF/RAS and TERT alterations, but not BRAF/RAS or TERT alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79-59.81, P = 0.009).This study suggested that comprehensively analysis of BRAF/RAS mutations, TERT promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC.CONCLUSIONSThis study suggested that comprehensively analysis of BRAF/RAS mutations, TERT promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC. Purpose Risk stratification based on somatic mutations in TERT promoter and BRAF / RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of BRAF / RAS mutations, TERT promoter mutations, and TERT promoter methylation in PTC. Methods The relationships of BRAF / RAS mutations, TERT promoter mutations, and TERT promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC. Results TERT promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with BRAF / RAS mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of BRAF / RAS and TERT alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both BRAF / RAS and TERT alterations had higher rates of tumor recurrence (13.6% vs 1.5%, P = 0.042) and disease progression (24.4% vs 3.3%, P < 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of BRAF / RAS and TERT alterations, but not BRAF / RAS or TERT alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79–59.81, P = 0.009). Conclusions This study suggested that comprehensively analysis of BRAF / RAS mutations, TERT promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC. PurposeRisk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation in PTC.MethodsThe relationships of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC.ResultsTERT promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with BRAF/RAS mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of BRAF/RAS and TERT alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both BRAF/RAS and TERT alterations had higher rates of tumor recurrence (13.6% vs 1.5%, P = 0.042) and disease progression (24.4% vs 3.3%, P < 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of BRAF/RAS and TERT alterations, but not BRAF/RAS or TERT alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79–59.81, P = 0.009).ConclusionsThis study suggested that comprehensively analysis of BRAF/RAS mutations, TERT promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC. Risk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation in PTC. The relationships of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC. TERT promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with BRAF/RAS mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of BRAF/RAS and TERT alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both BRAF/RAS and TERT alterations had higher rates of tumor recurrence (13.6% vs 1.5%, P = 0.042) and disease progression (24.4% vs 3.3%, P < 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of BRAF/RAS and TERT alterations, but not BRAF/RAS or TERT alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79-59.81, P = 0.009). This study suggested that comprehensively analysis of BRAF/RAS mutations, TERT promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC. |
| Author | Xue, Junyu Liu, Rengyun Hu, Guanghui Sang, Ye Chen, Mengke Hong, Shubin |
| Author_xml | – sequence: 1 givenname: Ye surname: Sang fullname: Sang, Ye organization: Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University – sequence: 2 givenname: Guanghui surname: Hu fullname: Hu, Guanghui organization: Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University – sequence: 3 givenname: Junyu surname: Xue fullname: Xue, Junyu organization: Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University – sequence: 4 givenname: Mengke surname: Chen fullname: Chen, Mengke organization: Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University – sequence: 5 givenname: Shubin surname: Hong fullname: Hong, Shubin organization: Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University – sequence: 6 givenname: Rengyun orcidid: 0000-0002-1408-2372 surname: Liu fullname: Liu, Rengyun email: liury9@mail.sysu.edu.cn organization: Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University |
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| CitedBy_id | crossref_primary_10_1016_j_surg_2024_05_058 crossref_primary_10_1007_s00405_024_08954_w crossref_primary_10_1186_s13000_024_01573_3 |
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| Keywords | DNA methylation mutation Prognosis Papillary thyroid cancer promoter mutation TERT promoter mutation BRAF mutation |
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| SSID | ssj0022267 |
| Score | 2.418712 |
| Snippet | Purpose
Risk stratification based on somatic mutations in
TERT
promoter and
BRAF
/
RAS
has been well established for papillary thyroid cancer (PTC), and there... Risk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is... PurposeRisk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is... |
| SourceID | proquest pubmed crossref springer |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 304 |
| SubjectTerms | Adult Aged Coexistence Diabetes DNA Methylation Endocrinology Female Humanities and Social Sciences Humans Internal Medicine Male Medicine Medicine & Public Health Metastases Middle Aged multidisciplinary Mutation Original Article Papillary thyroid cancer Prognosis Promoter Regions, Genetic Proto-Oncogene Proteins B-raf - genetics Risk Assessment Risk groups Science Telomerase - genetics Thyroid cancer Thyroid Cancer, Papillary - genetics Thyroid Cancer, Papillary - pathology Thyroid Neoplasms - genetics Thyroid Neoplasms - pathology Young Adult |
| Title | Risk stratification by combining common genetic mutations and TERT promoter methylation in papillary thyroid cancer |
| URI | https://link.springer.com/article/10.1007/s12020-024-03722-6 https://www.ncbi.nlm.nih.gov/pubmed/38356100 https://www.proquest.com/docview/3079951475 https://www.proquest.com/docview/2927209830 |
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