Detection of two novel mutations and relatively high incidence of H-RAS mutations in Vietnamese oral cancer

Murugan, Avaniyapuram Kannan; Hồng, Nguyễn Thị; Cuc, Tran Thi Kim; Hung, Nguyen Chan; Munirajan, Arasambattu Kannan; Ikeda, Masa‐Aki; Tsuchida, Nobuo

doi:10.1016/j.oraloncology.2009.05.638

Cited by 32 publications

(21 citation statements)

References 26 publications

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“…HRAS, a GTPase, has been proven to be a proto-oncogene and overaction drives the cells to uncontrolled division and thus carcinogenesis. The variant 'C' allele of the H-RAS T81C was founded to be associated with higher risk of oral cancer (Murugan et al, 2009;Jayaraman et al, 2012). NOTCH1, a transmembrane protein with repeated extracellular EGF domains and the NOTCH domains, works in multiple processes such as differentiation, proliferation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

Liu

Liu²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

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Section: Discussionmentioning

confidence: 99%

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

Liu

Liu²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…However, the incidence of RAS gene mutation is low in breast cancer and stomach cancer (24,25). A high incidence of RAS mutation, 18-30% of cases from India and Vietnam, has been reported and it has been associated with areca nut chewing (3,10,26) whereas lower frequencies of 4-5% were reported from UK and Japan (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

“…OSCC is considered to be the sixth most common cancer in the world (1). Smoking and alcohol consumption are major risks for HNSCC but only a fraction of people with these habits actually develop oral cancer, which implies that other genetic factors contribute to the pathogenesis of the disease (2,3). Infection by human papilloma virus has also emerged as a risk factor for HNSCC (4).…”

Section: Introductionmentioning

confidence: 99%

“…In view of the paucity of extensive studies regarding the status of BRAF and HRAS mutations in OSCC and to i) further assess the individual effect of the HRAS and BRAF mutations in OSCC, ii) to test whether their mutations are mutually exclusive, as in other cancers, and iii) to examine whether RAS is the activating factor of the PI3K signalling pathway previously reported (3,8,9) we performed a systematic molecular study in 86 clinically and histologically well-defined malignant tumors of oral squamous cell carcinoma, previously reported to lack PIK3CA hotspot mutations (15) and correlated the mutation status of HRAS and BRAF with age, gender, stage, histological grade and prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Novel mutations of the HRAS gene and absence of hotspot mutations of the BRAF genes in oral squamous cell carcinoma in a Greek population

et al. 2012

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Abstract. Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. The phosphatidylinositol 3 kinase (PI3K) signalling pathway has been reported to play an important role in OSCC. Since we have previously detected absence of hotspot PIK3CA gene mutations in the Greek population, we hypothesized that BRAF or HRAS may be activated as upstream effectors of the pathway. Furthermore, the status of the HRAS and BRAF mutations in OSCC has never been assessed before in the Greek population. Eighty-six primary paraffin-embedded tumors were screened for BRAF and HRAS hotspot mutations. In HRAS, two hotspot mutations in codon 12 (2.3%) and eight new genetic alterations were detected (8.6% overall). One new missense mutation, Alanine53Valine (Ala53Val), one silent mutation, two mutations in the 5'UTR region and four mutations in intron 1 were detected. No hotspot mutations in BRAF were found. A new silent mutation/polymorphism T1803C was detected at a percentage of 30%. This study is the first to report HRAS mutations in the Greek population. The results suggest that RAS is an important member of the PI3K signalling pathway and may play a role in the tumorigenesis of OSCC. IntroductionOral squamous cell carcinoma (OSCC) is a subset of head and neck squamous carcinoma (HNSCC) involving the oral tongue, upper gingival, lower gingival and alveolus, floor of the mouth, buccal mucosa, retromolar triangle, lip mucosa and hard palate. OSCC is considered to be the sixth most common cancer in the world (1). Smoking and alcohol consumption are major risks for HNSCC but only a fraction of people with these habits actually develop oral cancer, which implies that other genetic factors contribute to the pathogenesis of the disease (2,3). Infection by human papilloma virus has also emerged as a risk factor for HNSCC (4).The RAS family genes consist of three members, HRAS, KRAS and NRAS located on chromosomes 11, 12 and 1, respectively, encoding a 21 kDa membrane protein (p21), which possesses GTPase activity (5,6). HRAS has been shown to activate phosphatidylinositol 3 kinase (PI3K) more efficiently than KRAS and NRAS. Hotspots for RAS mutations are found in codons 12, 13 and 61, causing the mutant protein to lose its ability to exchange GTP with GDP thus remaining activated (7). RAS is also is an upstream regulator of PI3K. Thus an activated RAS could also activate the PI3K signalling pathway, which is shown to be activated in oral cancer (8,9). The incidence of RAS mutations varies greatly among different human tumors and different ethnicities. HRAS mutations are primarily found in cancers of the urinary tract and bladder.

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“…In OSCC, H-ras mutations are mainly detected in Asian populations, often associated with advanced stages of the tumor [23,81]. In Western populations, ras mutations in HNSCC are relatively rare events (<6%) compared to 99% in pancreatic cancer and approximately 40% in colorectal cancer [98,118,122].…”

Section: Ras Genementioning

confidence: 99%

Update of prognostic and predictive biomarkers in oropharyngeal squamous cell carcinoma: a review

Grimminger

Danenberg

2010

Eur Arch Otorhinolaryngol

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Oropharyngeal squamous cell carcinomas (OSCC) constitute about 5% of all cancers in the western world and the incidence and mortality rates of this tumor have shown little improvement over the last 30 years. Molecular targeted therapy, a promising strategy for the treatment of OSCC and other cancers, requires the understanding of specific molecular events of carcinogenesis and the different pathological, partly interrelated pathways. Extended knowledge of the prognostic or predictive value of molecular biomarkers in oropharyngeal cancer is necessary to allow a better characterization and classification of the tumor, improve the appraisal of clinical outcome and help to specify individual multimodal therapy with increased efficiency. This work affords an updated summary regarding recent data about tissue biomarkers in patients with OSCC, based on the six essential hallmarks of cancer described by Hanahan and Weinberg (Cell 100(1):57-70, 2000) providing the characterization of a malignant cell.

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Detection of two novel mutations and relatively high incidence of H-RAS mutations in Vietnamese oral cancer

Cited by 32 publications

References 26 publications

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

Novel mutations of the HRAS gene and absence of hotspot mutations of the BRAF genes in oral squamous cell carcinoma in a Greek population

Update of prognostic and predictive biomarkers in oropharyngeal squamous cell carcinoma: a review

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