Objective To investigate the role of BRAF^V600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results.Methods This study included 9837 patients who underwent US-FNA.We mainly analyze...Objective To investigate the role of BRAF^V600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results.Methods This study included 9837 patients who underwent US-FNA.We mainly analyzed 239 cases with benign or indeterminate cytology,but having a detection of BRAF^V600E mutation.BRAF^V600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction.Results In 93 nodules with benign cytology results but positive BRAF^V600E mutation,84 nodules were malignant.Based on the results,US-FNA combined with BRAF^V600E mutation analysis will improve sensitivity(Se=94.03%)and negative predictive value(NPV=2.69%)of the thyroid nodules diagnosis than using US-FNA alone(Se=71.03%,NPV=20.76%).Conclusion BRAFV600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV.When facing patients with benign or indeterminate cytology but positive BRAF^V600E mutation,thyroidectomy should be considered.展开更多
Radioiodine ablation（RIA） therapy is one of the most important treatments for papillary thyroid carcinoma（PTC）, but some patients who received 131 I have radioiodine-refractory disease caused by the decreased expr...Radioiodine ablation（RIA） therapy is one of the most important treatments for papillary thyroid carcinoma（PTC）, but some patients who received 131 I have radioiodine-refractory disease caused by the decreased expression of the Na^＋/I^- symporter（NIS）. BRAF^V600E mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF^V600E mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF^V600E mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance（A） values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF^V600E mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases（β=–0.0195, P=0.085）, but in the subgroup without hashimoto＇s thyroiditis（HT）, BRAF^V600E mutation could significantly inhibit the NIS expression（β=–0.0257, P=0.046）. The results indicate that BRAF^V600E mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.展开更多
Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic bi...Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma （PTMC） is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC （TCVPTMC）, multifocality, extrathyroidal extension （ETE） and lymph node metastasis （LNM）. A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were in- cluded in the meta-analysis, and 1143 （50.7%） of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size （OR： 1.64; 95% CI： 1.16-2.32）, multifocality （OR： 1.58; 95% CI： 1.25-2.00）, ETE （OR： 2.59; 95% CI： 2.03-3.29）, LNM （OR： 1.73; 95% CI： 1.14-2.62）, advanced stage （OR： 2.03; 95% CI： 1.14-3.64） and TCVPTMC （OR： 5.07; 95% CI： 1.49-17.27; P=0.009）. Additionally, the BRAF mutation was found to be not associated with age, gender, con- comitant hashimoto thyroiditis or nodular goiter （P〉0.05 for all）. This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, ad- vanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.展开更多
BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in ...BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.展开更多
Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma vira...Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma viral oncogene homolog B1) BRAF V600 E and TERT promoter mutations in differentiated thyroid carcinoma(DTC).The relationship between the two mutations and NIS/TSHR expression was also analyzed.Methods We have detected BRAF V600 E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC,52 cases of benign nodular goiter,and 31 cases of normal thyroid tissue.Results The BRAF V600 E mutation was detected in 142(62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma(PTC) and 1 case of follicular thyroid carcinoma(FTC)].TERT promoter mutations were detected in 18(7.9%) of 229 cases of DTC(14 cases of PTC and 4 cases of FTC),including the mutations C228T(0.9%) and C250T(7.0%),which were mutually exclusive.Moreover,11(61.1%) cases also harbored the BRAF V600 E mutation,which was not associated with gender,age,tumor size,lymph node metastasis,and recurrence risk stratification(P >0.05).The rate of TERT promoter mutation was higher in males,age ≥45,and in the middle/high-risk group(P <0.05),and the rate of simultaneous BRAF V600 E and TERT promoter mutations were higher in the middle/high-risk group(P <0.05).In addition,NIS positive rate in the concurrent BRAF V600 E and TERT promoter mutation group(45.5 %) was lower than in other groups(that is,the DTC group with BRAF V600 E or TERT promoter mutations(55.1%),the DTC group with no BRAF V600 E or TERT promoter mutation(57.5%),the nodules and normal group(75.9%);| r | = 0.171,P = 0.002).Conclusion TERT promoter mutations were lower in patients with DTC,with the C250 T mutation being the most common.The detection of BRAF V600 E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.展开更多
Objective The objective of this study was to analyze the correlation between BRAF^(V600E) and TERT promoter mutations and papillary thyroid microcarcinoma (PTMC) risk factors, and their importance in the risk assessme...Objective The objective of this study was to analyze the correlation between BRAF^(V600E) and TERT promoter mutations and papillary thyroid microcarcinoma (PTMC) risk factors, and their importance in the risk assessment of papillary thyroid microcarcinoma.Methods This study retrospectively analyzed 107 cases of PTMC, which were diagnosed after the surgery in the department of head and neck surgery in Gansu Province Tumor Hospital from October 2014to June 2016. The mutations of BRAFV^(600E) and TERT promoter were detected by PCR direct sequencing.We analyzed the data usingχ~2 test and binary Logistic regression analysis.Results Among 107 patients with PTMC, the BRAFV^(600E) and TERT promoter mutation rates were 68.2%and 11.2%, respectively. Single factor analysis showed that there was a significant difference between the presence of membrane invasion, lymph node metastasis, and BRAFV^(600E) mutations (P<0.01). The age,gender, thyroid capsular invasion, poor pathologic subtype, and lymph node metastasis of patients, was significantly associated with the TERT promoter mutation (P<0.05) and the coexistence of the BRAF^(V600E)and TERT promotor mutations; although, there was a difference between the association of these factors with the TERT promoter mutation and the association of these factors with the coexistence of the BRAF^(V600E)and TERT promotor mutations. The multifactorial analysis showed that the factors closely related to the BRAFV^(600E) mutation included capsular invasion (P=0.012) and lymph node metastasis (P=0.000). The following factors were closely associated with the TERT promoter mutant:male (P=0.004), aged <45 years(P=0.026), capsular invasion (P=0.004), pathological subtype (P=0.030), and lymph node metastasis (P=0.043). The following factors were closely related to the simultaneous mutation of BRAFV^(600E) and TERT:male (P=0.022), capsular invasion (P=0.023), poor pathological subtype (P=0.041), and lymph node metastasis (P=0.030).Conclusion The risk of recurrence increases significantly when mutations in BRAFV^(600E) and TERT promoters occur simultaneously in PTMC and may have adverse outcomes. Combined detection of BRAFV^(600E) and TERT promoter mutations is of great value in risk assessment of PTMC.展开更多
Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC ...Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC was downloaded and organized from The Cancer Genome Atlas (TCGA) via cBioPortal, then the gene mutation and clinical information of 402 PTC samples were analyzed. The correlation of BRAFV600E and RAS mutations with clinicopathological features and prognosis of PTC were subjected to univariate analysis. Secondly, we use Binary Logistic multivariate analysis to analyze the factors screened above. Results BRAFV600E mutation rate is 48.5% (195/402) and RAS mutation rate is 10.2% (41/402) in 402 cases of PTC. Univariate analysis showed that BRAFV600E mutation has nothing to do with age and sex of the patient. There is a significant correlation among BRAFV600E mutation and lymph node metastasis, extrathyroidal invasion, staging, recurrence, progression and pathological subtypes in PTC. There is no significant correlation among RAS and age, sex, staging, recurrence, progression. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC. Multivariate logistic regression analysis indicated that there is a significant correlation among BRAFV600E mutation and extrathyroidal invasion, pathological subtypes in PTC. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC.ConclusionThe mutation rate of BRAFV600E was significantly higher than that of RAS in PTC. Mutations in BRAFV600E and RAS can be used as predictors of prognosis in PTC.展开更多
Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expre...Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expression and activity thus has recently become a target for drug therapy. Several melanoma cell lines were exposed to inhibitors of Src activity despite their broad specificity. To examine the particular activity of Src in human melanoma cells, we used SU6656, the selective inhibitor of Src family protein kinases. The activity of Src and cell proliferation were suppressed in HBL human cells, wild type melanoma cells and in SK-MEL-5 human melanoma cells harboring mutant BRAF V600E, upon their treatment with SU6656. The suppression of Src kinase activity had not inhibitory effects on Akt/PKB activity in SK-MEL-5 cells, which we have previously found in HBL cells. This may indicate that changes of Src involvement in the control of Akt/PKB activity and its downstream signaling could be induced by BRAF V600E mutation in SK-MEL-5 cells.展开更多
采用突变等位基因特异性扩增法(mutant allele specific amplication,MASA-PCR)检测了125例甲状腺石蜡包埋组织中BRAFV600E点突变(包括94例甲状腺癌,15例甲状腺腺瘤,15例结节性甲状腺肿和1例癌旁正常组织),探讨甲状腺乳头状癌(PTC)与其...采用突变等位基因特异性扩增法(mutant allele specific amplication,MASA-PCR)检测了125例甲状腺石蜡包埋组织中BRAFV600E点突变(包括94例甲状腺癌,15例甲状腺腺瘤,15例结节性甲状腺肿和1例癌旁正常组织),探讨甲状腺乳头状癌(PTC)与其临床病理学特征之间的关系。结果发现,仅在PTC和1例甲状腺未分化癌中检测到BRAFV600E突变,PTC中突变率为68.4%(57/83),主要见于经典型PTC和微小癌,其突变率分别为73%(52/71)和2/3,在其它类型的甲状腺癌及良性病变中均未检测到BRAFV600E突变。临床病理资料显示,患者发病平均年龄为45岁,突变率在40岁以上者显著高于40以下者(χ2=4.69,P<0.05),而与性别、淋巴结转移、慢性淋巴细胞浸润无显著关系(P<0.05)。结果显示,1)BRAFV600E突变仅发生于PTC和部分未分化癌,是PTC中较常见的遗传学事件,可为PTC的发生机制提供新的视点。2)BRAFV600E突变主要见于经典型PTC和微小癌,可能是甲状腺乳头状癌表型的重要决定因素之一。展开更多
文摘Objective To investigate the role of BRAF^V600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results.Methods This study included 9837 patients who underwent US-FNA.We mainly analyzed 239 cases with benign or indeterminate cytology,but having a detection of BRAF^V600E mutation.BRAF^V600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction.Results In 93 nodules with benign cytology results but positive BRAF^V600E mutation,84 nodules were malignant.Based on the results,US-FNA combined with BRAF^V600E mutation analysis will improve sensitivity(Se=94.03%)and negative predictive value(NPV=2.69%)of the thyroid nodules diagnosis than using US-FNA alone(Se=71.03%,NPV=20.76%).Conclusion BRAFV600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV.When facing patients with benign or indeterminate cytology but positive BRAF^V600E mutation,thyroidectomy should be considered.
基金supported by Hubei Natural Science Foundation of China(No.2014CKB519)
文摘Radioiodine ablation（RIA） therapy is one of the most important treatments for papillary thyroid carcinoma（PTC）, but some patients who received 131 I have radioiodine-refractory disease caused by the decreased expression of the Na^＋/I^- symporter（NIS）. BRAF^V600E mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF^V600E mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF^V600E mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance（A） values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF^V600E mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases（β=–0.0195, P=0.085）, but in the subgroup without hashimoto＇s thyroiditis（HT）, BRAF^V600E mutation could significantly inhibit the NIS expression（β=–0.0257, P=0.046）. The results indicate that BRAF^V600E mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.
文摘Summary： Recent studies have demonstrated that the BRAFv600E mutation is associated with aggres- sive clinicopathological features of papillary thyroid carcinoma （PTC）. However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma （PTMC） is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC （TCVPTMC）, multifocality, extrathyroidal extension （ETE） and lymph node metastasis （LNM）. A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were in- cluded in the meta-analysis, and 1143 （50.7%） of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size （OR： 1.64; 95% CI： 1.16-2.32）, multifocality （OR： 1.58; 95% CI： 1.25-2.00）, ETE （OR： 2.59; 95% CI： 2.03-3.29）, LNM （OR： 1.73; 95% CI： 1.14-2.62）, advanced stage （OR： 2.03; 95% CI： 1.14-3.64） and TCVPTMC （OR： 5.07; 95% CI： 1.49-17.27; P=0.009）. Additionally, the BRAF mutation was found to be not associated with age, gender, con- comitant hashimoto thyroiditis or nodular goiter （P〉0.05 for all）. This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, ad- vanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.
文摘BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
基金Supported by a grant from the Beijing Medical Awards Foundation(No.YJHYXK YJJ-206)
文摘Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma viral oncogene homolog B1) BRAF V600 E and TERT promoter mutations in differentiated thyroid carcinoma(DTC).The relationship between the two mutations and NIS/TSHR expression was also analyzed.Methods We have detected BRAF V600 E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC,52 cases of benign nodular goiter,and 31 cases of normal thyroid tissue.Results The BRAF V600 E mutation was detected in 142(62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma(PTC) and 1 case of follicular thyroid carcinoma(FTC)].TERT promoter mutations were detected in 18(7.9%) of 229 cases of DTC(14 cases of PTC and 4 cases of FTC),including the mutations C228T(0.9%) and C250T(7.0%),which were mutually exclusive.Moreover,11(61.1%) cases also harbored the BRAF V600 E mutation,which was not associated with gender,age,tumor size,lymph node metastasis,and recurrence risk stratification(P >0.05).The rate of TERT promoter mutation was higher in males,age ≥45,and in the middle/high-risk group(P <0.05),and the rate of simultaneous BRAF V600 E and TERT promoter mutations were higher in the middle/high-risk group(P <0.05).In addition,NIS positive rate in the concurrent BRAF V600 E and TERT promoter mutation group(45.5 %) was lower than in other groups(that is,the DTC group with BRAF V600 E or TERT promoter mutations(55.1%),the DTC group with no BRAF V600 E or TERT promoter mutation(57.5%),the nodules and normal group(75.9%);| r | = 0.171,P = 0.002).Conclusion TERT promoter mutations were lower in patients with DTC,with the C250 T mutation being the most common.The detection of BRAF V600 E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.
基金Supported by a grant from the Science and Technology Plan Projects of Lanzhou(No.2017-4-75)
文摘Objective The objective of this study was to analyze the correlation between BRAF^(V600E) and TERT promoter mutations and papillary thyroid microcarcinoma (PTMC) risk factors, and their importance in the risk assessment of papillary thyroid microcarcinoma.Methods This study retrospectively analyzed 107 cases of PTMC, which were diagnosed after the surgery in the department of head and neck surgery in Gansu Province Tumor Hospital from October 2014to June 2016. The mutations of BRAFV^(600E) and TERT promoter were detected by PCR direct sequencing.We analyzed the data usingχ~2 test and binary Logistic regression analysis.Results Among 107 patients with PTMC, the BRAFV^(600E) and TERT promoter mutation rates were 68.2%and 11.2%, respectively. Single factor analysis showed that there was a significant difference between the presence of membrane invasion, lymph node metastasis, and BRAFV^(600E) mutations (P<0.01). The age,gender, thyroid capsular invasion, poor pathologic subtype, and lymph node metastasis of patients, was significantly associated with the TERT promoter mutation (P<0.05) and the coexistence of the BRAF^(V600E)and TERT promotor mutations; although, there was a difference between the association of these factors with the TERT promoter mutation and the association of these factors with the coexistence of the BRAF^(V600E)and TERT promotor mutations. The multifactorial analysis showed that the factors closely related to the BRAFV^(600E) mutation included capsular invasion (P=0.012) and lymph node metastasis (P=0.000). The following factors were closely associated with the TERT promoter mutant:male (P=0.004), aged <45 years(P=0.026), capsular invasion (P=0.004), pathological subtype (P=0.030), and lymph node metastasis (P=0.043). The following factors were closely related to the simultaneous mutation of BRAFV^(600E) and TERT:male (P=0.022), capsular invasion (P=0.023), poor pathological subtype (P=0.041), and lymph node metastasis (P=0.030).Conclusion The risk of recurrence increases significantly when mutations in BRAFV^(600E) and TERT promoters occur simultaneously in PTMC and may have adverse outcomes. Combined detection of BRAFV^(600E) and TERT promoter mutations is of great value in risk assessment of PTMC.
基金National Natural Science Foundation of China.Project No:81302577.
文摘Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC was downloaded and organized from The Cancer Genome Atlas (TCGA) via cBioPortal, then the gene mutation and clinical information of 402 PTC samples were analyzed. The correlation of BRAFV600E and RAS mutations with clinicopathological features and prognosis of PTC were subjected to univariate analysis. Secondly, we use Binary Logistic multivariate analysis to analyze the factors screened above. Results BRAFV600E mutation rate is 48.5% (195/402) and RAS mutation rate is 10.2% (41/402) in 402 cases of PTC. Univariate analysis showed that BRAFV600E mutation has nothing to do with age and sex of the patient. There is a significant correlation among BRAFV600E mutation and lymph node metastasis, extrathyroidal invasion, staging, recurrence, progression and pathological subtypes in PTC. There is no significant correlation among RAS and age, sex, staging, recurrence, progression. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC. Multivariate logistic regression analysis indicated that there is a significant correlation among BRAFV600E mutation and extrathyroidal invasion, pathological subtypes in PTC. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC.ConclusionThe mutation rate of BRAFV600E was significantly higher than that of RAS in PTC. Mutations in BRAFV600E and RAS can be used as predictors of prognosis in PTC.
基金supported by grant NT11231-3/2010 from the Ministry of Health of the Czech Republic
文摘Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expression and activity thus has recently become a target for drug therapy. Several melanoma cell lines were exposed to inhibitors of Src activity despite their broad specificity. To examine the particular activity of Src in human melanoma cells, we used SU6656, the selective inhibitor of Src family protein kinases. The activity of Src and cell proliferation were suppressed in HBL human cells, wild type melanoma cells and in SK-MEL-5 human melanoma cells harboring mutant BRAF V600E, upon their treatment with SU6656. The suppression of Src kinase activity had not inhibitory effects on Akt/PKB activity in SK-MEL-5 cells, which we have previously found in HBL cells. This may indicate that changes of Src involvement in the control of Akt/PKB activity and its downstream signaling could be induced by BRAF V600E mutation in SK-MEL-5 cells.
文摘采用突变等位基因特异性扩增法(mutant allele specific amplication,MASA-PCR)检测了125例甲状腺石蜡包埋组织中BRAFV600E点突变(包括94例甲状腺癌,15例甲状腺腺瘤,15例结节性甲状腺肿和1例癌旁正常组织),探讨甲状腺乳头状癌(PTC)与其临床病理学特征之间的关系。结果发现,仅在PTC和1例甲状腺未分化癌中检测到BRAFV600E突变,PTC中突变率为68.4%(57/83),主要见于经典型PTC和微小癌,其突变率分别为73%(52/71)和2/3,在其它类型的甲状腺癌及良性病变中均未检测到BRAFV600E突变。临床病理资料显示,患者发病平均年龄为45岁,突变率在40岁以上者显著高于40以下者(χ2=4.69,P<0.05),而与性别、淋巴结转移、慢性淋巴细胞浸润无显著关系(P<0.05)。结果显示,1)BRAFV600E突变仅发生于PTC和部分未分化癌,是PTC中较常见的遗传学事件,可为PTC的发生机制提供新的视点。2)BRAFV600E突变主要见于经典型PTC和微小癌,可能是甲状腺乳头状癌表型的重要决定因素之一。
