scholarly journals Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer

2006 ◽  
Vol 119 (10) ◽  
pp. 2322-2329 ◽  
Author(s):  
Shuiying Hu ◽  
Dingxie Liu ◽  
Ralph P. Tufano ◽  
Kathryn A. Carson ◽  
Eli Rosenbaum ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Tumor Suppressor Genes ◽  
Aberrant Methylation ◽  
Papillary Thyroid ◽  
Tumor Aggressiveness ◽  
Suppressor Genes

scholarly journals Mitogen-Inducible Gene-6 Is a Multifunctional Adaptor Protein with Tumor Suppressor-Like Activity in Papillary Thyroid Cancer

2011 ◽  
Vol 25 (2) ◽  
pp. 373-373
Author(s):  
Chi-Iou Lin ◽  
Jinyan Du ◽  
Wen Shen ◽  
Edward E. Whang ◽  
David B. Donner ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Papillary Thyroid Cancer ◽  
Adaptor Protein ◽  
Papillary Thyroid ◽  
Inducible Gene

scholarly journals Mitogen-Inducible Gene-6 Is a Multifunctional Adaptor Protein with Tumor Suppressor-Like Activity in Papillary Thyroid Cancer

2011 ◽  
Vol 32 (1) ◽  
pp. 157-158
Author(s):  
Chi-Iou Lin ◽  
Jinyan Du ◽  
Wen Shen ◽  
Edward E. Whang ◽  
David B. Donner ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Papillary Thyroid Cancer ◽  
Adaptor Protein ◽  
Papillary Thyroid ◽  
Inducible Gene

A Methylation Profile of Tumor Suppressor Genes Predicts a Poorer Survival in Patients with Refractory Anemia with Ringed Sideroblasts.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2780-2780
Author(s):  
Ana Valencia ◽  
Jose Cervera ◽  
Esperanza Such ◽  
Esther Gamero ◽  
Mariam Ibañez ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Methylation Profile ◽  
Refractory Anemia ◽  
Aberrant Methylation ◽  
Gene Methylation ◽  
Suppressor Genes ◽  
Ring Sideroblasts ◽  
Aberrant Gene

Abstract Abstract 2780 Poster Board II-756 Patients with refractory anemia with ring sideroblasts (RARS) are considered to have good prognosis and anemia is usually managed with best supportive care and erythroid stimulating agents. Nowadays, no specific molecular marker related to outcome and disease progression has been identified. Several genes involved in cell cycle and apoptosis that may become inactivated by aberrant hypermethylation have been identified in patients with myelodysplastic syndromes (MDS) but the significance of a methylation profile (studying several genes at the same time) in RARS is unknown, mainly because the number of patients with RARS in published reports is rather low. To assess the implication of aberrant methylation in RARS, we studied the methylation status of 25 sequences of a set of tumor suppressor genes in 40 patients (median age 70 yr, 25 male gender) with RARS according to FAB criteria [WHO classification, RARS in 22 patients (55%); refractory citopenia with multilineage dysplasia and ring sideroblasts, 18 (45%)] by means of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. The MS-MLPA procedure (SALSA MLPA kit ME001, MRC-Holland, Amsterdam, The Netherlands) has been developed for detecting in a semi-quantitative manner changes in the methylation status of 25 tumor suppressor genes in a single experiment. Briefly, approximately 50 ng of DNA were denatured and hybridized with MLPA probes. Subsequently, the probes were ligated in half of every sample, whereas for the rest of the sample, ligation was combined with an endonuclease HhaI digestion resulting in ligation of the methylated sequences only. PCR was performed as described by the manufacturer, and then separated by capillary gel electrophoresis and quantified using the Genemapper software (ABI 310, Applied Biosystems, Foster City, CA). Quantification of the methylation status was done by dividing the peak area with the combined areas of the control probes lacking the target sequence of the HhaI. Finally, the relative peak area of each target probe from the digested sample was compared with those obtained from the undigested sample. Aberrant methylation was scored when the calculated methylation percentage was >10%. To validate the MS-MLPA method the methylation status of CDKN2B was also analyzed by methylation-specific PCR (MSP). Actuarial curves of OS were built by Kaplan-Meier method and differences between curves compared with log-rank tests. Small numbers precluded the use of multivariate methodology. The MS-MLPA analysis detected methylation of at least one gene in 17 patients (42.5%). The genes aberrantly methylated were CDKN2B (n = 8, 20%), RASSF1 (n = 7, 17%), RARB (n = 3, 7.5%), CDH13 (n = 3, 7.5%) and FHIT (n = 2; 5%). Of the 17 patients, five (12%) presented methylation in two genes (RASSF1-FHIT in 2, RASSF1-RARB in 1, RASSF1-CDH13 in 1, and CDKN2B-CDH13 in 1, who was the only patient who progressed to AML). The presence of aberrant gene methylation was not significantly associated with any clinical or biological characteristic or WHO morphological subtype. Patients with aberrant gene methylation had a significantly shorter overall survival (OS) than patients without methylated genes (median OS, 72 mo vs 114 mo, respectively; P = 0.03). Patients with hemoglobin level below 10 g/dL and platelet count below 150 ×109/L also had a significantly poorer OS (P= 0.01 and P= 0.02, respectively). As the majority of probes used in the MS-MPLA method detect methylation in only one CpG pair, the results of CDKN2B methylation were validated by MSP, which yielded the same methylation results than with MS-MPLA methodology. The 8 patients with methylated CDKN2B show a trend for a shorter survival than the remaining 32 with unmethylated CDKN2B (median 72 mo vs 114 mo, P = 0.08). The results of this study indicate that aberrant methylation of several tumor suppressor genes is observed in a substantial proportion of patients with RARS. As occurs in patients with high-risk MDS, our results suggest that aberrant gene methylation confers a poor prognosis in RARS, but these data and their potential independent value require confirmation in larger series that employ multivariate methods. Finally, these findings provide a strong rationale for the use of hypomethylating agents (e.g., azacitidine or decitabine) in patients with RARS. This work has been partially supported by ISCIII grants RD06/0020/0031 and CA08/00141. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mitogen-Inducible Gene-6 Is a Multifunctional Adaptor Protein with Tumor Suppressor-Like Activity in Papillary Thyroid Cancer

2011 ◽  
Vol 96 (3) ◽  
pp. E554-E565 ◽  
Author(s):  
Chi-Iou Lin ◽  
Jinyan Du ◽  
Wen T. Shen ◽  
Edward E. Whang ◽  
David B. Donner ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Papillary Thyroid Cancer ◽  
Adaptor Protein ◽  
Papillary Thyroid ◽  
Inducible Gene

scholarly journals BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer

2005 ◽  
Vol 90 (12) ◽  
pp. 6373-6379 ◽  
Author(s):  
Mingzhao Xing ◽  
William H. Westra ◽  
Ralph P. Tufano ◽  
Yoram Cohen ◽  
Eli Rosenbaum ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Thyroid Cancer ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Advanced Tumor Stage ◽  
Papillary Thyroid ◽  
Clinical Prognosis ◽  
Mutation Status ◽  
Predictors Of Recurrence

Context: Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer. Objective: The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC. Design, Setting, and Subjects: In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed. Main Outcome Measure: Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured. Results: We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3–29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1–14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease. Conclusions: In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.

Differential miRNAs expression in papillary thyroid cancer is associated with clinico-pathological features and BRAF mutation

2014 ◽  
Author(s):  
Esmeralda Castelblanco ◽  
Veronica Rosado ◽  
Montserrat Martinez ◽  
Maria Dolores Santos ◽  
Veronica Mancikova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Pathological Features ◽  
Papillary Thyroid ◽  
Mirnas Expression
Sign in / Sign up

Export Citation Format

Share Document