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Biallelic inactivation of the p16-Gen in a metachronous triple carcinoma in the oropharyngeal region


, : Biallelic inactivation of the p16-Gen in a metachronous triple carcinoma in the oropharyngeal region. Laryngo- Rhino- Otologie 83(1): 55-60

Recent studies have shown that most Dutch families with atypical multiple-mole melanoma (FAMMM) have a 19-bp deletion (p16-Leiden) in exon 2 of the p16 gene. Apart from reports on metachronous pancreatic tumors, other cancer types have never been described in such families. Due to heterozygous p16-Leiden constitution, our proband with multiple head and neck carcinomas was a suitable model for studying the type of p16 inactivation according to the Knudson-two-hit model. p16 mutations in exons 1 and 2 were determined using PCR-SSCP-Sequencing analysis. p16 methylation was assessed by methylation-specific PCR. All three metachronous (larynx, pharynx, oral cavity) tumors had a methylated p16 promotor. The p16 protein loss detected by immunohistochemistry clearly confirmed a complete loss of p16 tumor suppressor function. Thus, all three tumors exhibited biallelic inactivation of p16, caused by aberrant methylation of the p16 promotor. This is the first report on p16-Leiden mutation in head and neck cancer. We provide evidence that the somatic methylation of p16 promotor is associated with the germline transmission of p16-Leiden mutation. This is an example for the rare event of in which aberrant methylation acting as the 'second hit' in a familial cancer syndrome. Our results show that this epigenetic event is equivalent to genetic alterations (mutation/LOH) confirming the Knudson's hypothesis for tumor suppressor gene inactivation.

US$19.90

PMID: 14740307

DOI: 10.1055/s-2004-814111


Other references

Castaigne, P.; Cathala, H.P., 1953: Recurring confusing episodes. La Revue du Praticien 3(27): 1973-1977

Lee, J.; Miller, B.T.; Damjanović, A.; Brooks, B.R., 2014: Constant pH Molecular Dynamics in Explicit Solvent with Enveloping Distribution Sampling and Hamiltonian Exchange. We present a new computational approach for constant pH simulations in explicit solvent based on the combination of the enveloping distribution sampling (EDS) and Hamiltonian replica exchange (HREX) methods. Unlike constant pH methods based on var...

Marom, S.; Gilboa-Schechtman, E.; Aderka, I.M.; Weizman, A.; Hermesh, H., 2009: Impact of depression on treatment effectiveness and gains maintenance in social phobia: a naturalistic study of cognitive behavior group therapy. Background: The impact of depression on cognitive behavioral group therapy (CBGT) for social phobia (SP) in a naturalistic outpatient setting was examined after treatment termination and at 1-year follow-up. Methods: Consecutive SP outpatients (N=...

Sikorski, A.F., 2017: iCellular and Molecular Biology Letters goes open access with BioMed Central. Cellular & Molecular Biology Letters 21: 1-1

Mrsny R.J.; Volwerk J.J.; Griffith O.H., 1986: A simplified procedure for lipid phosphorus analysis shows that digestion rates vary with phospholipid structure. A simplified procedure for lipid digestion, well suited for handling a large number of samples, was used to analyze a variety of ceommon phosphollipids. This procedure involves digestion of phospholipids in percholoric acid at 130.degree. C with m...

Hellberg, A.; Poole, J.; Olsson, M.L., 2002: Molecular basis of the globoside-deficient Pk blood group phenotype. Identification of four inactivating mutations in the UDP-N-acetylgalactosamine:globotriaosylceramide 3-b-N-acetylgalactosaminyltransferase gene. The Journal of Biological Chemistry 277(33): 455-9

Brooks, J.S., 1972: Which surface for asepsis?. Canadian Hospital 49(4): 29-29

Torregrossa, M.M.; Sanchez, H.; Taylor, J.R., 2010: D-cycloserine reduces the context specificity of pavlovian extinction of cocaine cues through actions in the nucleus accumbens. Extinction therapy has been proposed as a method to reduce the motivational impact of drug-associated cues to prevent relapse. Cue extinction therapy, however, takes place in a novel context (e.g., treatment facility), and is unlikely to be effect...

Dawkins K.D.; Cotter L.; Gibson D.G., 1984: Assessment of mitral bjork shiley prosthetic dys function using digitized m mode echo cardiography. Digitized M mode echocardiograms were analyzed in 22 patients with possible Bjork-Shiley mitral prosthetic dysfunction. Patients with paraprosthetic mitral regurgitation had a significantly greater shortening fraction, an increased peak rate of di...

Baram, P.; Yuan, L.; Mosko, M.M., 1966: Studies on the transfer of human delayed-type hypersensitivity. I. Partial purification and characterization of two active components. Journal of Immunology 97(3): 407-420