BRAF mutations in papillary carcinomas of the thyroid

Fukushima, Toshihiko; Suzuki, Shinichi; Mashiko, Miyuki; Ohtake, Tohru; Endo, Yoshiyuki; Takebayashi, Yuji; Sekikawa, Koji; Hagiwara, Koichi; Takenoshita, Seiichi

doi:10.1038/sj.onc.1206739

Cited by 270 publications

(190 citation statements)

References 10 publications

(9 reference statements)

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…The T1799A transversion in exon 15 has been associated with distinct histological subtypes of PTC (the highest prevalence was shown for the tall cell variant with 77%, followed by the conventional type with 60%). 24,28,[34][35][36][37][38][39][40] The lowest prevalence was reported for the follicular variant (12%) (reviewed by Xing 20 ). A literature search revealed seven cases of diffuse sclerosing variant of PTC examined for BRAF V599E mutation so far (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

et al. 2007

View full text Add to dashboard Cite

Diffuse sclerosing variant of papillary thyroid carcinoma (PTC) is a rare tumour with a characteristic morphology as well as a strong preponderance for younger female patients. The T1799A missense mutation in exon 15 of the BRAF gene and RET/PTC rearrangement have been identified as the dominant genetic tumour initiation events in the pathogenesis of PTC leading to a constitutive activation of the RAS-RAF-MAPK pathway. In order to elucidate the pathogenesis of diffuse sclerosing variant of PTC, the prevalence of BRAF mutation and RET/PTC were determined by RT-polymerase chain reaction and DNA-sequence analysis in tumour samples of seven patients with this variant (all female, age range 15-61 years, mean 33.3 years) without prior radiation exposure. None of these cases showed a BRAF mutation. RET/PTC1 (two out of seven) and RET/PTC3 (one out of seven), which have been shown in large PTC series to comprise together more than 90% of RET/PTC types, were found in o50% of the cases investigated. All seven samples expressed the RET tyrosine kinase domain but lacked its extracellular domain potentially suggesting the existence of rare types of RET/PTC rearrangement in the four remained cases of diffuse sclerosing variant of PTC. Regarding this subtype, our study confirmed the paradigm of a mutual exclusivity between RET/PTC and BRAF in PTC. Additionally, this rare variant of papillary thyroid carcinoma may represent a tumour type susceptible to RET-targeted therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Mutual exclusivity between these two mutations was also seen in thyroid cancer (Fukushima et al 2003, Soares et al 2003, Frattini et al 2004. These and other studies , Lima et al 2004, Nikiforova et al 2004, Vasil'ev et al 2004) similarly showed mutual exclusivity between BRAF mutation and RET/PTC rearrangements in thyroid cancer.…”

Section: Introductionmentioning

confidence: 95%

“…The only other BRAF mutation reported in thyroid tumors was the K601E mutation found in two benign thyroid adenomas (Soares et al 2003, Lima et al 2004) and three follicular-variant PTCs . The mutations in exon 11 of the BRAF gene found in other human cancers were not found in thyroid cancer (Cohen et al 2003, Fukushima et al 2003, Namba et al 2003, Frattini et al 2004, Perren et al 2004, Puxeddu et al 2004. A rare but interesting genetic alteration that can also cause constitutive activation of BRAF is the recently reported in vivo fusion of the BRAF gene with AKAP9 gene through a paracentric inversion of the long arm of chromosome 7.…”

Section: Introductionmentioning

confidence: 99%

BRAF mutation in thyroid cancer

Xing¹

2005

Endocrine Related Cancer

1,158

976

View full text Add to dashboard Cite

Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2 years ago, rapid advancements have been made. BRAF mutation is the most common genetic alteration in thyroid cancer, occurring in about 45% of sporadic papillary thyroid cancers (PTCs), particularly in the relatively aggressive subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role, as demonstrated by transgenic mouse studies that showed BRAF mutation-initiated development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in thyroid cancer. The T1799A BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer and is a specific diagnostic marker for this cancer when identified in cytological and histological specimens. This mutation is associated with a poorer clinicopathological outcome and is a novel independent molecular prognostic marker in the risk evaluation of thyroid cancer. Moreover, preclinical and clinical evaluations of the therapeutic value of novel specific mitogen-activated protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic.Endocrine-Related Cancer (2005) 12 245-262

show abstract

“…When multi-step carcinogenesis is taken into account, a considerable number of anaplastic carcinomas with BRAF mutations should be found. In previous reports, however, the frequency of the BRAF mutation was only about 10% on average and ranged from 0 to 63% (Fukushima et al, 2003;Namba et al, 2003;Nikiforova et al, 2003;Begum et al, 2004;Soares et al, 2004;Xing et al, 2004;Quiros et al, 2005). Among these studies, some reported that the BRAF mutation is found frequently only in anaplastic carcinomas with a papillary carcinoma component, although these studies have examined only four or five cases.…”

mentioning

confidence: 94%

BRAFV600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas

et al. 2007

View full text Add to dashboard Cite

Frequency of a BRAF V600E mutation in anaplastic thyroid carcinoma, which is thought to be derived mainly from papillary carcinoma by multi-step carcinogenesis, is much lower than that in papillary carcinomas. To clarify this phenomenon, we analysed BRAF V600E mutation in 20 cases of anaplastic carcinoma and 13 accompanying differentiated carcinomas. Among twenty cases of anaplastic carcinomas, nine and four accompanied papillary and follicular carcinomas, respectively. BRAF V600E mutation was found in four (20%) cases. BRAF V600E mutation was found in three of nine (33.3%), none of four and one of seven (14.3%) anaplastic carcinomas with papillary carcinoma, follicular carcinoma and without differentiated components, respectively. All three papillary carcinomas accompanied by anaplastic carcinoma with a BRAF V600E mutation were also shown to have a BRAF V600E mutation. In summary, BRAF V600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma, and the low frequency of BRAF V600E mutation in anaplastic carcinoma was thought to be due to the low frequency of anaplastic carcinomas with papillary carcinoma. These findings raise a question about the classical model of anaplastic transformation and suggest some roles of thyroid cancer stem cells in the generation of anaplastic carcinoma. Thyroid carcinomas are thought to be generated from normal thyroid follicular cells (thyrocytes) by multi-step carcinogenesis (Farid et al, 1994). According to this hypothesis, anaplastic carcinomas are generated from both follicular and papillary carcinomas by genomic changes, such as mutations in TP53. Follicular carcinomas are generated from follicular adenomas, while papillary carcinomas are derived from some unknown precursor cells that are generated from normal thyrocytes. Recently, a somatic point mutation in the BRAF gene has been identified as the most common genetic event in papillary thyroid carcinoma . Most of the tumours with a mutation harboured a thymine-to-adenine transversion at nucleotide position 1799, which results in a valine-to-glutamic acid substitution at residue 600 (V600E). Previous reports indicated that BRAF mutations in thyroid tumours are generally restricted to papillary carcinoma, and usually there is no mutation in other types of well-differentiated thyroid cancers, including follicular carcinoma, Hürthle carcinoma and medullary carcinoma, as well as in benign thyroid tumours. The frequency of the mutations in papillary carcinomas is ranged from 29 to 83% of papillary carcinoma (Xing, 2005).It remains controversial whether this gene is also mutated in anaplastic thyroid carcinomas. In iodine-sufficient areas such as Japan, papillary carcinoma accounts for 90% of thyroid differentiated carcinomas and follicular carcinoma is rare (Hay, 1990). When multi-step carcinogenesis is taken into account, a considerable number of anaplastic carcinomas with BRAF mutations should be found. In previous reports, however, the frequency of the BRAF mutation was only about 10% on average...

show abstract

BRAF mutations in papillary carcinomas of the thyroid

Cited by 270 publications

References 10 publications

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

BRAF mutation in thyroid cancer

BRAFV600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas

Contact Info

Product

Resources

About