Mutations of the BRAF gene in squamous cell carcinoma of the head and neck

Weber, Anette; Langhanki, Larissa; Sommerer, Florian; Markwarth, Annett; Wittekind, Christian; Tannapfel, Andrea

doi:10.1038/sj.onc.1206705

Cited by 122 publications

(115 citation statements)

References 19 publications

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“…Our report is consistent with the emerging evidence that while BRAF mutations are common in certain cancer types, such as colorectal and thyroid cancers and melanomas, they are rare to absent in many other malignancies, such as pancreatic, gastric, renal cell, and head and neck cancers. [26][27][28][29][30] In fact, even within one given cancer type, there exist dramatic differences in frequency of mutations based on tissue origin; thus while 80% of cutaneous melanomas harbor BRAF mutations, these are essentially absent in melanomas of the uveal tract. 19,31 The rarity (or absence) or BRAF mutations is biliary cancers implies that the V599E mutation is unlikely to be a useful biomarker for early detection of these cancers in bile fluids.…”

Section: Discussionmentioning

confidence: 99%

The V599E BRAF mutation is uncommon in biliary tract cancers

et al. 2004

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Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation-V599E-accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector s assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/ RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study.

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Section: Discussionmentioning

confidence: 99%

The V599E BRAF mutation is uncommon in biliary tract cancers

et al. 2004

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“…After microdissection, 22,23 methylation-specific PCR (MSP) was used to investigate the methylation status of the promoter region of the BLU, RASSF1A and SEMA3B genes. Microdissection was performed as described previously.…”

Section: Methylation Analysismentioning

confidence: 99%

“…Microdissection was performed as described previously. 22,23 After an initial bisulfite treatment to modify the DNA, PCR was performed to distinguish methylated from unmethylated DNA as described by Herman et al 24 Briefly, 2 mg of genomic DNA was denatured with 0.3 M NaOH; 10 mM hydroquinone and 3 M sodium bisulfite were added and incubated for 16 hr at 508C. Afterward, modified DNA was purified using the Wizard DNA purification resin (Promega, Madison, WI) followed by desulfonating in 0.3 M NaOH and subsequent ethanol precipitation and resuspension in 30-50 ml water.…”

Section: Methylation Analysismentioning

confidence: 99%

Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors

Tischoff

Markwarth

Witzigmann

et al. 2005

Intl Journal of Cancer

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Previously, the RASSF1A, BLU and SEMAPHORIN 3B (SEMA3B) candidate tumor suppressor genes on chromosome 3p21.3 were found to be inactivated and downregulated by genetic and epigenetic changes in lung cancer. We analyzed the methylation status of RASSF1A, BLU and SEMA3B in 35 hepatocellular carcinomas (HCCs) and 15 cholangiocarcinomas (CCs) by methylationspecific PCR and loss of heterozygosity (LOH) at 3p21.3 after microdissection. The presence of mRNA transcripts was confirmed by semiquantitative PCR. SEMA3B hypermethylation was found in 29/35 HCCs (83%) and in all (15/15) patients with CC. BLU promoter hypermethylation was detected in 7/35 (20%) HCCs and 3/15 (20%) CCs. In 2 corresponding specimens of hepatitis B virus-related liver cirrhosis, BLU methylation was also observed, but not in uninvolved normal liver tissue. RASSF1A was methylated in 21/35 HCCs (60%) and in 10/15 CCs (67%). LOH at 3p21.3 occurred in 8/35 (23%) HCCs and 3/15 (20%) CCs. The presence of hypermethylation was statistically associated with LOH of SEMA3B and correlated with downregulation of mRNA transcripts. SEMA3B transcripts increased upon treatment of HCC cell lines with the demethylation compound 5-aza-2-deoxycytidine. In conclusion, our data indicate that 2-hit gene silencing of SEMA3B through epigenetic changes and allele loss is a common and important event in the carcinogenesis of malignant liver tumors. ' 2005 Wiley-Liss, Inc.Key words: hepatocellular carcinoma; cholangiocarcinoma; methylation; loss of heterozygosity; BLU; SEMA3B; RASSF1A Primary liver cancer is one of the most frequent carcinomas worldwide. Besides hepatocellular carcinoma (HCC), accounting for 80-90% of all primary liver cancers, cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. The short arm of chromosome 3 has been shown to exhibit loss of heterozygosity (LOH) in several types of cancer, including ovarian, kidney, lung, nasopharyngeal and also liver cancer. 1,2 In particular, overlapping homozygous deletions in lung cancers have been identified in region 3p21.3. 3,4 In HCC, LOH of chromosome 3p occurred in about 30% of the patients. 5,6 Several genes located on chromosome 3p have been studied in HCC as well as CC and include RASSF1A on 3p21.31, FHIT at 3p14.2, RIZ1, VHL at 3p25. 7-10 These results directed an intensive search for possible tumor suppressor genes located in the 3p21 region for one or more genes that could function as gatekeepers in molecular pathogenesis of human cancers. A group of candidate tumor suppressor genes (designated BLU, SEMAPHORIN 3B, or RASSF1A) has recently been mapped to this critical gene-rich region. 2,[11][12][13] SEMAPHORIN 3B (SEMA3B) is a member of the semaphorin family, which is also located on 3p21.3. Semaphorins are a family of signaling molecules initially identified to play a role in axonal guidance and can be classified as either membrane-bound (classes 1, 4, 5 and 6) or secreted (classes 2 and 3). 14 The receptors for the class 3 semaphorins are also known as neuropilin receptors. The intr...

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“…1,2 Mutations of K-ras have been found in 80-90% of pancreatic cancers, 3 30-60% of colorectal cancers, 4,5 20-30% of non-small cell lung cancers 6 and 5% of squamous cell carcinomas of the head and neck. 7 Therefore, K-ras oncogene represents an attractive target for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

et al. 2010

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Mutations of K-ras have been found in 30-60% of colorectal carcinomas and are believed to be associated with tumor initiation, tumor progression and metastasis formation. Therefore, silencing of mutant K-ras expression has become an attractive therapeutic strategy for colorectal cancer treatment. The aim of our study was to investigate the effect of microRNA (miRNA) molecules directed against K-ras (miRNA-K-ras) on K-ras expression level and the growth of colorectal carcinoma cell line LoVo in vitro and in vivo. In addition, we evaluated electroporation as a gene delivery method for transfection of LoVo cells and tumors with plasmid DNA encoding miRNA-K-ras (pmiRNA-K-ras). Results of our study indicated that miRNAs targeting K-ras efficiently reduced K-ras expression and cell survival after in vitro electrotransfection of LoVo cells with pmiRNA-K-ras. In vivo, electroporation has proven to be a simple and efficient delivery method for local administration of pmiRNA-K-ras molecules into LoVo tumors. This therapy shows pronounced antitumor effectiveness and has no side effects. The obtained results demonstrate that electrogene therapy with miRNA-K-ras molecules can be potential therapeutic strategy for treatment of colorectal cancers harboring K-ras mutations.

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Mutations of the BRAF gene in squamous cell carcinoma of the head and neck

Cited by 122 publications

References 19 publications

The V599E BRAF mutation is uncommon in biliary tract cancers

The V599E BRAF mutation is uncommon in biliary tract cancers

Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors

MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

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