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Array-based comparative genomic hybridization (array-CGH) has good potential for the high-throughput identification of genetic aberrations in cell genomes. In the course of a program to screen a panel of oral squamouscell carcinoma (OSCC), cell lines for genomic copynumber aberrations by array-CGH using our in-house arrays, we identified a 3-Mb homozygous deletion at 10p12 in 1 of 18 cell lines (5.6%). Among seven genes located within this region, expression of PRTFDC1 mRNA was not detected in 50% (9/18) or decreased in 5.6% (1/18) of OSCC cell lines, but detected in normal oral epithelia and restored in gene-silenced OSCC cells without its homozygous loss after treatment with 5-aza-2 0 -deoxycytidine. Among 17 cell lines without a homozygous deletion, the hypermethylation of the PRTFDC1 CpG island, which showed promoter activity, was observed in all nine cell lines with no or reduced PRTFDC1 expression (52.9%). Methylation of this CpG island was also observed in primary OSCC tissues (8/47, 17.0%). In addition, restoration of PRTFDC1 in OSCC cells lacking its expression inhibited cell growth in colony-formation assays, whereas knockdown of PRTFDC1 expression in OSCC cells expressing the gene promoted cell growth. These results suggest that epigenetic silencing of PRTFDC1 by hypermethylation of the CpG island leads to a loss of PRTFDC1 function, which might be involved in squamous cell oral carcinogenesis.

Objective: To assess the influence of different dentoskeletal patterns on the availability of interradicular spaces and to determine the safe zones for miniscrew implant placement. Materials and Methods: Periapical radiographs of 60 subjects with skeletal Class I, II, or III patterns were examined. For each interradicular site, the areas and distances at 3, 5, 7, 9, and 11 mm from the alveolar crest were measured. Results: In the maxilla, the greatest interradicular space was between the second premolar and the first molar. In the mandible, the greatest interradicular space was between the first and second molars, followed by the first and second premolars. Significant differences in interradicular spaces among the skeletal patterns were observed. Maxillary interradicular spaces, particularly between the first and second molars, in the subjects with skeletal Class II patterns, were greater than those in the subjects with skeletal Class III patterns. In contrast, in the mandible, interradicular spaces in the subjects with skeletal Class III patterns were greater than those in the subjects with skeletal Class II patterns. Conclusions: For all skeletal patterns, the safest zones were the spaces between the second premolar and the first molar in the maxilla, and between the first and second premolars and between the first and second molars in the mandible. (Angle Orthod. 2011;81:397-403.)

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Previously, we have reported frequent silencing of the expression of LRP1B by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma. As the same events might be involved in the development/progression of OSCC, we examined intragenic homozygous deletions, expression levels, and methylation status in the CpG island of this gene. Homozygous deletion was detected in only 1 of 18 (5.6%) OSCC lines, whereas the expression of LRP1B mRNA was silenced in 8 of 17 (47.1%) OSCC lines without homozygous deletion. An inverse correlation between mRNA expression and methylation status of the LRP1B CpG island was clearly observed in OSCC lines, and LRP1B mRNA expression was restored by treatment with 5-aza-dCyd. Frequent methylation of the LRP1B promoter was also observed in primary OSCC. Taken O ral cancer, predominantly OSCC, is the most common head and neck neoplasm, affecting >400 000 people worldwide every year.(1,2) Despite advances in surgical techniques, chemotherapy, and radiation, 50% of patients die of the disease or complications from it within 5 years.(3) Moreover, OSCC has a severe impact on quality of life through impairments of swallowing and speaking or esthetic disorders. Despite recent progress in the diagnosis and therapeutic methods for OSCC, the prognosis has not improved, reflecting the ineffectiveness of current treatment regimens.(4) An improved understanding of the molecular pathogenesis of OSCC is urgently needed to identify new targets and strategies for effective therapy.(5,6) However, the molecular mechanisms of the progression of OSCC are still unknown.The carcinogenesis of OSCC is thought to be a multistep phenomenon in which a variety of genetic alterations can be segregated into early to late stages.(7) Recently, in addition, evidence has emerged that epigenetic mechanisms, such as altered DNA methylation patterns, play a significant role in the silencing of tumor suppressor genes and contribute to malignant transformation during carcinogenesis.(8) Although several genes, for example, p14, p15, p16, RASSF1A, VHL, hMLH1, and MGMT, have been reported to be silenced by aberrant DNA methylation, (9)(10)(11)(12)(13)(14)(15)(16) some of them were infrequently methylated in OSCC compared with other tumors. In order to create the b.est possible panel of markers for the prediction of outcome, sensitivity to chemotherapy and radiation, and disease status OSCC, more candidates for tumor-suppressor genes targeted by promoter methylation will no doubt be tested in this disease. (16) Recently, we have reported frequent inactivation of the LRP1B (2q22.1) through intragenic homozygous deletion or promoter hypermethylation in ESCC. (17) In the study reported here, homozygous deletion of LRP1B was observed in only 1 of 18 OSCC cell lines, whereas silencing of the expression of LRP1B mRNA through methylation of the promoter was observed in 8 of 18 OSCC cell lines, suggesting that LRP1B is mainly inactivated through an epigenetic mechanism in OSCC. Frequent hypermethylation of the LRP1B promote...

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