Alvimar Afonso Barbosa

Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, representing ˜90% of all oral carcinomas and accounting for 3–5% of all malignancies. The WWOX gene (WW‐domain containing oxidoreductase) is a candidate tumor suppressor gene located at 16q23.3–24.1, spanning the second most common fragile site, FRA16D. In this report, the role of the WWOX gene was investigated in 20 tumors and 10 normal oral mucosas, and we demonstrated an altered WWOX gene in 50% (10/20) of OSCCs. Using nested RT‐PCR, mRNA transcription was altered in 35% of the tumors, with the complete absence of transcripts in 2 samples as well as absence of exons 6–8 (2 tumors), exon 7 (1 tumor), exon 7 and exon 6–8 (1 tumor) and partial loss of exons 8 and 9 (1 tumor). To determine if the aberrant transcripts were translated, Western blots were performed in all samples; however, only the normal protein was detected. By immunohistochemistry, a reduction in Wwox protein expression was observed, affecting 40% of the tumors when compared with normal mucosa. In addition, a novel somatic mutation (S329F) was found. The presence of alterations in mRNA transcription correlated with the reduced expression of Wwox protein in the tumors. These results show that the WWOX gene is frequently altered in OSCC and may contribute to the carcinogenesis processes in oral cancer.

Abstract 2728: Clonal nature of benign and malignant salivary gland neoplasms

The pathogenesis of salivary gland neoplasms (SGN) has not been established. There is a real debate on clonality issues and all the definitive evidence is on the side of polyclonal tumor origin. Evidence that many tumor types may be polyclonal in origin has been published. Despite all this body of evidence, scientists have incorporated the clonal theory proposed by Knudson (1985) and only strengthen these results (and do not discuss contrary findings), because they think it is expected. There are few clonality studies on benign salivary neoplasms and almost no data on malignant neoplasms. The HUMARA assay was used in the present study to investigate the clonality of 27 samples of SGN (17 benign and ten malignant). Briefly, samples were digested with HhaI and HpaII methylation-sensitive enzymes and a PCR carried out. Eighteen out of 27 cases revealed monotypy, while three were non-informative and six showed heterotypy, indicating a true polyclonality. In summary, our results show evidence that a subset of SGN might be clonal in origin, while some samples are polyclonal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2728. doi:10.1158/1538-7445.AM2011-2728