<i>BRAF</i> mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma

Costa, Ângela M.; Herrero, Agustín; Fresno, Manuel; Heymann, Jonas J.; Álvarez, José Antonio; Cameselle-Teijeiro, José; García-Rostán, Ginesa

doi:10.1111/j.1365-2265.2007.03077.x

Cited by 117 publications

(93 citation statements)

References 56 publications

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“…Recently, Alzahrani and Xing (2013) also found that BRAF gene mutations in thyroid cancer could predict lymph node metastasis, which is consistent with our results. Furthermore, multivariate regression analysis also suggested that lymph node metastasis and the presence of BRAF V600E mutations were independent predictors for tumor prognosis, which is also in agreement with the literature (Costa et al, 2008;Henderson et al, 2009). As BRAF gene mutations and lymph node metastasis are closely associated with tumor recurrence, pre-operative detection of the mutation and conventional lymph node dissection may help to reduce the recurrence rate (Bozec et al, 2011;Alzahrani and Xing, 2013).…”

Section: Discussionsupporting

confidence: 78%

“…Although several studies have found that BRAF gene mutations are closely correlated with thyroid cancer prognosis, few of these studies have come from China (Costa et al, 2008;Gong et al, 2009;Henderson et al, 2009;Xing et al, 2009;Howell et al, 2011). In the present study, we demonstrated that the BRAF V600E mutation is closely related with age, tumor staging, and clinical prognosis.…”

Section: Discussionsupporting

confidence: 58%

“…This mutation is rarely found in normal thyroid tissue or in benign types of thyroid diseases (Davies et al, 2002;Xing, 2005;Kebebew et al, 2007;DeLuca et al, 2008;Kim et al, 2012). Several studies have also found significant associations between the mutation with clinicopathological features such as patient age, extrathyroidal invasion, lymph node metastasis, and tumor stage, which may help clinical prognoses of PTC (Costa et al, 2008;Xing et al, 2009;Gong et al, 2009;Howell et al, 2011). Furthermore, a small molecule targeting a downstream kinase of BRAF has also attracted attention recently (Bollag et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Efficient detection of the V600E mutation of the BRAF gene in papillary thyroid carcinoma using multiplex allele-specific polymerase chain reaction combined with denaturing high-performance liquid chromatography

Gong¹,

Gong²,

Yang³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Mutations in the V-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) play an important role in the pathogenesis of papillary thyroid cancer (PTC). In this study, a BRAF V600E mutation was detected in formalin-fixed and paraffin-embedded PTC samples using multiplex allele-specific polymerase chain reaction and denaturing high-performance liquid chromatography. The sensitivity of the assays was validated in two cell lines, K1 and RO82-W-1, which were respectively positive and negative for the mutation. The method enabled detection of very low concentrations Efficient detection of BRAF V600E mutation in thyroid cancer (~1%) of the mutation, with positive findings obtained in 119 of the 187 samples (63.6%). The mutation was not detected in 20 cases of benign thyroid diseases. The presence of the mutation was significantly associated with ages >45 years, the tumor-nodesmetastasis stage, region of metastasis, and clinical outcome (P < 0.05). Although no correlation was found between the mutation and lymph node metastasis, the proportions of patients carrying a mutation differed significantly between central and lateral cervical lymph node metastasis (P < 0.05). Multivariate logistic regression analysis also indicated the presence of mutation, tumor size, and cervical lymph node metastasis to be independent predictors for recurrence and distant metastasis. We conclude that a high proportion of PTC cases likely harbors the BRAF V600E mutation. This mutation can be used as an independent factor for predicting the recurrence and distal metastasis of PTC tumors.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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Efficient detection of the V600E mutation of the BRAF gene in papillary thyroid carcinoma using multiplex allele-specific polymerase chain reaction combined with denaturing high-performance liquid chromatography

Gong¹,

Gong²,

Yang³

et al. 2013

Genet. Mol. Res.

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“…ATC tumors present a significant prevalence of RAS (6-55%) and BRAF mutations (24-50%) (13,14,107). By contrast, RET/PTC, NTRK and PPARγ-PAX8 rearrangements are rarely observed in these undifferentiated tumors, supporting the hypothesis that DTCs associated with these rearrangements do not usually progress to anaplastic form (108,109). BRAF V600E mutation is typically found in ATC tumors which contain areas of well-differentiated PTC, but also in poorly differentiated and anaplastic tumor areas.…”

Section: Anaplastic Thyroid Carcinomamentioning

confidence: 55%

“…Its action occurs by removing a phosphate group from the inositol ring of PIP3, which reduces the downstream activity of the AKT kinase, thereby inducing cell cycle arrest, apoptosis, or both (113). Several genetic alterations in the PTEN suppressor gene have been described in ATCs: 12% present a mutated form (106,108), 28% gene silencing (114) and 69% the hypermethylated PTEN gene (115). These alterations lead to PTEN inactivation by different mechanisms, with a prominent role in the pathogenesis of follicular epithelium-derived thyroid carcinomas, particularly in the most aggressive or undifferentiated forms (114,115).…”

Section: Anaplastic Thyroid Carcinomamentioning

confidence: 99%

Signaling pathways in follicular cell-derived thyroid carcinomas

Romitti

Ceolin

Siqueira

et al. 2012

International Journal of Oncology

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Abstract. Thyroid carcinoma is the most common malignant endocrine neoplasia. Differentiated thyroid carcinomas (DTCs) represent more than 90% of all thyroid carcinomas and comprise the papillary and follicular thyroid carcinoma subtypes. Anaplastic thyroid carcinomas correspond to less than 1% of all thyroid tumors and can arise de novo or by dedifferentiation of a differentiated tumor. The etiology of DTCs is not fully understood. Several genetic events have been implicated in thyroid tumorigenesis. Point mutations in the BRAF or RAS genes or rearranged in transformation (RET)/papillary thyroid carcinoma (PTC) gene rearrangements are observed in approximately 70% of papillary cancer cases. Follicular carcinomas commonly harbor RAS mutations and paired box gene 8 (PAX8)-peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Anaplastic carcinomas may have a wide set of genetic alterations, that include gene effectors in the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and/or β-catenin signaling pathways. These distinct genetic alterations constitutively activate the MAPK, PI3K and β-catenin signaling pathways, which have been implicated in thyroid cancer development and progression. In this context, the evaluation of specific genes, as well as the knowledge of their effects on thyroid carcinogenesis may provide important information on disease presentation, prognosis and therapy, through the development of specific tyrosine kinase targets. In this review, we aimed to present an updated and comprehensive review of the recent advances in the understanding of the genetic basis of follicular cell-derived thyroid carcinomas, as well as the molecular mechanisms involved in tumor development and progression.

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Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine‐needle aspirates: A quality‐assurance metric for evaluating diagnostic performance in a cytopathology laboratory

Gokozan

Dilcher

Alperstein

et al. 2021

Cancer Cytopathology

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Background Molecular testing (MT) of thyroid fine‐needle aspiration (FNA)‐derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. Methods Neoplasia‐associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS‐like mutations (HRAS, NRAS, or KRAS mutations or non‐V600E BRAF mutations), or other mutations. Results Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1‐8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4‐9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8‐89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS‐like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. Conclusions Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.

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BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma

Abstract: BRAF(V600E)'alone' does not represent a marker for poor outcome, however, when associated with alterations in other genes identifies a subset of PTCs with increased risk of recurrence and decreased survival.

Cited by 117 publications

References 56 publications

Efficient detection of the V600E mutation of the BRAF gene in papillary thyroid carcinoma using multiplex allele-specific polymerase chain reaction combined with denaturing high-performance liquid chromatography

Efficient detection of the V600E mutation of the BRAF gene in papillary thyroid carcinoma using multiplex allele-specific polymerase chain reaction combined with denaturing high-performance liquid chromatography

Signaling pathways in follicular cell-derived thyroid carcinomas

Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine‐needle aspirates: A quality‐assurance metric for evaluating diagnostic performance in a cytopathology laboratory

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