The Clinical Utility of BRAF and RAS Mutations


BRAF and RAS gene mutations that are often considered diagnostic or prognostic predictors of thyroid cancer (TC) generate skepticism among scholars in the last decade. However, a certain degree of confusion exists as some academics find in a sufficient number of patients with thyroid cancer mutations of BRAF V600E or RAS (Basolo et al. 4197; Howell 928). In this paper, it will be argued that mutations of BRAF and RAS genes do not constitute reliable diagnostic or prognostic markers of thyroid cancer.

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Literature Review on BRAF

Many researchers agree that TC patients emerge with a high prevalence of BRAF mutations, yet it is only one of the factors influencing the development of this cancer type (Czarniecka et al. 495). Yet, as genetic abnormalities in BRAF are also uncovered in patients with other cancer types, it cannot be reliably used as a standalone predictor of TC (Li et al. 4559; Czarniecka et al. 495). A recent study by Haymart identified that TERT promoter mutations were also discovered along with BRAF in patients with TC and PTC, which undermines the positions of BRAF as an independent predictor of those cancers (433).

A similar study performed by Shen et al. demonstrated that in older patients there seems to be no association between the BRAF gene abnormalities and papillary thyroid cancer mortality (438). Fakhruddin et al. also report that NRAS mutations may be responsible for TC as well as BRAF, which also does not speak to the exclusive diagnostic or prognostic qualities of the latter (1). Thus, presently, there is a tendency to use a combination of several gene mutations to predict and forecast TC instead of considering BRAF alone.

Literature Review on RAS

According to Howell, RAS mutation prevalence reaches 53% in patients suffering from different forms of TC, which, considering the clinical challenges in diagnosing TCs, poses significant aid in this process (929). On the other hand, several scientists notice that follicular adenomas also reveal a high prevalence of RAS in patients, which makes the usage of RAS as a predictor for TC ambiguous (Medici et al. 184; Howell et al. 927; Xing 1). Xing also notices that in combination with other gene variations RAS can be predictive of TC, yet the sole reliance on RAS alone is far from being helpful in either diagnostic or prognostic analysis (1).

Dou et al. suggest that proto-oncogene (HRAS) is also found in people suffering from thyroid cancer and specifies that there might be more variations of the mutation (4511). This study concludes that there is a need for more extensive studies on genetic predictors of TC before any of the mutations can be reliably used in diagnosing or predicting those cancers (Dou 4516). Therefore, while some regard should be given to RAS, there is a sufficient reason to believe that other markers need to be used to reliably identify and treat thyroid cancer.


It appears that neither RAS nor BRAF could be held fully accountable for the oncogenesis of thyroid cancers alone. The majority of studies, both recent and historical, suggesting that despite the prevalence of these particular mutations in patients with TC, there is currently no conclusive data on other possible factors. Scientists find evidence of new mutations responsible for TC emergence, which appears to undermine the utility of RAS and BRAF in diagnosing and predicting TC development. There is a strong indication that a combination of mutations may be a more reliable predictor of those cancers, yet further research is required.

Works Cited

Basolo, Fulvio, et al. “Correlation between the BRAF V600E Mutation and Tumor Invasiveness in Papillary Thyroid Carcinomas Smaller than 20 Millimeters: Analysis of 1060 Cases.” The Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 2010, pp. 4197-4205.

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Czarniecka, Agnieszka, et al. “BRAF V600E Mutation in Prognostication of Papillary Thyroid Cancer (PTC) Recurrence.” Gland Surgery, vol. 5, no. 2016, pp. 495-505.

Dou, Rui, et al. “Identification of a Novel HRAS Variant and Its Association with Papillary Thyroid Carcinoma.” Oncology Letters, vol. 15, no. 2018, pp. 4511-4516.

Fakhruddin, Najla, et al. “BRAF and NRAS Mutations in Papillary Thyroid Carcinoma and Concordance in BRAF Mutations Between Primary and Corresponding Lymph Node Metastases.” Scientific Reports, vol. 7, no. 2017, p. 1-11.

Haymart, Megan R. “Is BRAF V600E Mutation the Explanation for Age-Associated Mortality Risk in Patients With Papillary Thyroid Cancer?” Journal of Clinical Oncology, vol. 36, no. 2017, pp. 433-34.

Howell, Gina M., et al. “RAS Mutations in Thyroid Cancer.” The Oncologist, vol. 18, no. 2013, pp. 926-32.

Li, Carol, et al. “BRAF V600E Mutation and Its Association with Clinicopathological Features of Papillary Thyroid Cancer: A Meta-Analysis.” The Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 2012, pp. 4559-4570.

Medici, Marco, et al. “The Variable Phenotype and Low-Risk Nature of RAS-Positive Thyroid Nodules.” BMC Medicine, vol. 2015, p. 184-193.

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Shen, Xiaopei, et al. “Patient Age–Associated Mortality Risk Is Differentiated by BRAF V600E Status in Papillary Thyroid Cancer.” Journal of Clinical Oncology, vol. 36, no. 2017, pp. 438–45.

Xing, Mingzhao. “Clinical Utility of RAS Mutations in Thyroid Cancer: A Blurred Picture Now Emerging Clearer.” BMC Medicine, vol. 14, no. 2016, pp. 1-4.

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StudyCorgi. 2021. "The Clinical Utility of BRAF and RAS Mutations." March 21, 2021.


StudyCorgi. (2021) 'The Clinical Utility of BRAF and RAS Mutations'. 21 March.

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