Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer

Brait, Mariana; Loyo, Myriam; Rosenbaum, Eli; Ostrow, Kimberly Laskie; Markova, Alina; Papagerakis, Silvana; Zahurak, Marianna; Goodman, Steven; Zeiger, Martha A.; Sidransky, David; Umbricht, Christopher B.; Hoque, Mohammad O.

doi:10.4161/epi.20524

Cited by 55 publications

(49 citation statements)

References 40 publications

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“…RASSF1A promoter methylation correlated inversely with K-Ras and B-Raf mutation status in cervical adenocarcinomas [122] and thyroid cancers [123][124][125]. RASSF1A methylation was also shown recently to inversely correlate with TP53 mutations [120], suggesting that they likely have independent mechanisms in tumourigenesis.…”

Section: Epigenetic Regulation Of the Rassfsmentioning

confidence: 82%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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a b s t r a c tGenetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFjB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

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Section: Epigenetic Regulation Of the Rassfsmentioning

confidence: 82%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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“…51 According to the research, these results limit the usefulness of this gene as a diagnostic marker; additionally, the hypermethylation in the tumors in neoplastic relevance is questionable. Our understanding of the physiological role of the gene is still at an early stage.…”

Section: Dapk1mentioning

confidence: 99%

Expression profiles of selected genes in tumors and matched surgical margins in oral cavity cancer: Do we have to pay attention to the molecular analysis of the surgical margins?

Strzelczyk¹,

Krakowczyk²,

Gołąbek³

et al. 2018

Adv Clin Exp Med

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“…No information has been found in the available literature on the association between RASSF1A methylation level in cytology specimens of thyroid nodules and their sonographic characteristics. Most published studies on RASSF1A methylation analyse thyroid tissue specimens obtained from surgical samples [33][34][35].…”

Section: Prace Oryginalnementioning

confidence: 99%

Ocena częstości występowania mutacji genów BRAF, KRas oraz metylacji genu RASSF1A w wolu guzkowym na podstawie badania materiału cytologicznego uzyskanego drogą biopsji aspiracyjnej cienkoigłowej

Koziołek

Bińczak-Kuleta

Stepaniuk

et al. 2015

Endokrynologia Polska

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Frequency assessment of BRAF mutation, KRas mutation, and RASSF1A methylation in nodular goitre based on fine-needle aspiration cytology specimens Ocena częstości występowania mutacji genów BRAF, KRas oraz metylacji genu RASSF1A w wolu guzkowym na podstawie badania materiału cytologicznego uzyskanego drogą biopsji aspiracyjnej cienkoigłowej AbstractIntroduction: Standard pre-operative diagnosis of nodular goitre is not always conclusive. The decision about nodular goitre surgery is increasingly based on molecular methods. The aim of the study was to determine BRAF T1799A mutation and KRas proto-oncogene mutation, and the analysis of RASSF1A promoter methylation level in cytological material obtained from FNAB specimens of thyroid nodules. Material and methods:The study population consisted of 85 women and 12 men. The study material was genomic DNA isolated from peripheral blood and thyroid bioptates. Pyrosequencing was used for the evaluation of RASSF1 methylation level. KRas mutation was investigated with Sanger sequencing. BRAF mutation was analysed by standard methods of real-time amplification detection (real-time PCR) with the use of specific starters surrounding the mutated site. Results: A significant positive correlation was demonstrated between mean methylation of four CpG islands of RASSF1A gene and thyroid tumour volume and its largest diameter (p < 0.05). KRas mutation was not detected in any of the 97 patients. In 7/85 subjects (8.2%) BRAF mutation was observed. In 6/7 patients with BRAF mutation, FNAB of thyroid nodules confirmed a benign nature of the lesions; the material was non-diagnostic in one patient, and papillary thyroid cancer was diagnosed on the basis of postoperative histopathology assessment. Conclusions:The results of genetic tests reported in our study indicate that the presence of BRAF mutation or higher RASSF1A methylation levels in FNAB cytology specimens of benign lesions may be useful in the assessment of oncological risk, while the evaluation of KRas proto-oncogene mutation is not a valuable test in pre-operative diagnosis of nodular goitre. (Endokrynol Pol 2015; 66 (5): 384-393)

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Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer

Abstract: These authors contributed equally to this work.

Cited by 55 publications

References 40 publications

RASSF tumor suppressor gene family: Biological functions and regulation

RASSF tumor suppressor gene family: Biological functions and regulation

Expression profiles of selected genes in tumors and matched surgical margins in oral cavity cancer: Do we have to pay attention to the molecular analysis of the surgical margins?

Ocena częstości występowania mutacji genów BRAF, KRas oraz metylacji genu RASSF1A w wolu guzkowym na podstawie badania materiału cytologicznego uzyskanego drogą biopsji aspiracyjnej cienkoigłowej

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