H-ras gene mutations in salivary gland pleomorphic adenomas

Milašin, Jelena; Pujić, Natalija; Dedović, Nasta; Gavric, M.; Vranić, Vesna; Petrović, Vesna; Minić, Arsa J.

doi:10.1016/s0901-5027(05)80668-x

Cited by 23 publications

(11 citation statements)

References 12 publications

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“…Our results on H-ras mutations incidence in PA, though lower (17%) than the results previously reported for the same population (35%) by Milasin et al (35), are not negligible and point to a possible invol - Contrasting with oncogene analysis, polymorphisms analysis gave more satisfactory results. Only a few association studies trying to correlate gene polymorphisms and risk of PA have been carried out and none concerning survivin and MMP-9 gene promoter SNPs.…”

Section: Discussioncontrasting

confidence: 57%

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Nikolic¹,

Aničić²,

Tepavčević³

et al. 2013

Journal of Medical Biochemistry

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Summary Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomor- phic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detec- tion). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p<0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c- myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter poly- morphisms represent susceptibility factors for the develop- ment of PAs in the Serbian population.

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Section: Discussioncontrasting

confidence: 57%

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Nikolic¹,

Aničić²,

Tepavčević³

et al. 2013

Journal of Medical Biochemistry

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“…No K-ras mutations were demonstrated in cases with adenoid cystic carcinoma, pleomorphic adenoma, and pleomorphic carcinoma, 14,17 whereas mutated H-ras genes were present in 35% of the pleomorphic adenomas. 13 In a previous study (submitted for publication), salivary gland carcinomas were investigated for the presence of point mutations in H-ras and K-ras genes, and the frequencies of the H-ras and K-ras activation were 21% and 8%, respectively. Of the 11 mucoepidermoid carcinomas included, there were detectable ras mutations in 5 tumors (45%) and K-ras activation in 1 (9%).…”

Section: Discussionmentioning

confidence: 99%

“…The stud-ies to date are quite limited, and only a few reports of isolated cases of the alterations in ras, RB1, and p53 genes in some salivary gland tumors have been published. 13,14 Of all malignant salivary gland tumors, mucoepidermoid carcinoma is the most common, accounting for up to 9% of these lesions. 15 A previous investigation (submitted for publication) of ras activation in salivary gland tumors demonstrated the relevance of H-ras mutation to mucoepidermoid carcinoma, which prompted us to investigate the mutational status of this gene in a large series of the tumors to determine whether mutational activation of H-ras is an important molecular event in the development and progression of mucoepidermoid carcinomas.…”

Section: R As Genes Encode For a P21mentioning

confidence: 99%

H-ras gene mutations in salivary gland mucoepidermoid carcinomas

Yoo

Robinson

2000

Cancer

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“…12 This limited effect of ras is surprising because expression of the activated form of genes for the Ras family of GTPases, H-Ras, K-Ras, and N-Ras has been associated with the pathogenesis of a wide variety of human tumors, including salivary gland neoplasm. [13][14][15][16] Indeed, the H-ras gene has been found mutated in 35% of the salivary gland pleomorphic adenomas 14 and in adenocarcinomas of the parotid glands, albeit with a slight lower incidence (23%). 17 Leaky transgenic expression of oncogenes in salivary gland tissues when using a variety of promoters can also result in a low incidence of salivary gland tumors.…”

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confidence: 99%

Rapid Development of Salivary Gland Carcinomas upon Conditional Expression of K-ras Driven by the Cytokeratin 5 Promoter

Raimondi

Vitale‐Cross

Amornphimoltham

et al. 2006

The American Journal of Pathology

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We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice. Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week. All major salivary glands were affected, as well as a set of previously undescribed buccal accessory salivary glands located on the apex of the masseter muscle, close to the oral angle. The tumors appear to arise from the cytokeratin 5-positive basal cell compartment. Myoepithelial cells participated in the hyperplasias but not in carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas did not accumulate immunoreactive p53 but are positive for p63, as assayed by immunohistochemistry using an antibody against the N terminus of ⌬N p63, a splice variant of p63 that can inhibit p53 transcriptional activity. In this study, we provide evidence that the ras oncogene, targeted to a specifically sensitive cell compartment within the salivary glands, can trigger a series of event that are sufficient for full carcinogenesis. (Am J Pathol

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H-ras gene mutations in salivary gland pleomorphic adenomas

Cited by 23 publications

References 12 publications

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

H-ras gene mutations in salivary gland mucoepidermoid carcinomas

Rapid Development of Salivary Gland Carcinomas upon Conditional Expression of K-ras Driven by the Cytokeratin 5 Promoter

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