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This review is a survey of prospective studies on the clinical performance of posterior resin composites published between 1996 and 2002. Material, patient- and operator-specific data, observation periods, isolation methods of the operative field, and failure rates are detailed in tables. The data were evaluated statistically in order to assess the role of materials (filler size, bonding system, base materials [e.g. glass ionomer cements], and lining materials), study design, and personnel on failure rates. The primary reasons for composite failure were secondary caries, restoration fracture, and marginal defects. The influence of different commercial material brands on failure rates was not evaluated due to the great variety of test substances and the lack of material-specific documentation. Effects of the isolation method of the operative field (rubber dam or cotton rolls) and the professional status of operators (university or general dentist) on composite failure rates were not found to be significant. Observation periods varied from 1 to 17 years, and failure rates ranged between 0% and 45%. A linear correlation between failure rate and observation period was found (P<0.0001). Thirteen of 24 studies were terminated after 3 years, while seven studies continued for more than 10 years, indicating that favourable results for composite materials are frequently based on short-term results, despite higher dropout rates in longer studies. To determine accurately the risk for patients, long-term, randomised, controlled clinical trials of treatment outcomes with composites used in posterior teeth are clearly needed.

The congenital ®brosarcoma t(12;15)(p13;q25) rearrangement splices the ETV6 (TEL) gene on chromosome 12p13 in frame with the NTRK3 (TRKC) neurotrophin-3 receptor gene on chromosome 15q25. Resultant ETV6-NTRK3 fusion transcripts encode the helix ± loop ± helix (HLH) dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. We show here that ETV6-NTRK3 homodimerizes and is capable of forming heterodimers with wild-type ETV6. Moreover, ETV6-NTRK3 has PTK activity and is autophosphorylated on tyrosine residues. To determine if the fusion protein has transforming activity, NIH3T3 cells were infected with recombinant retroviral vectors carrying the full-length ETV6-NTRK3 cDNA. These cells exhibited a transformed phenotype, grew macroscopic colonies in soft agar, and formed tumors in severe combined immunode®cient (SCID) mice. We hypothesize that chimeric proteins mediate transformation by dysregulating NTRK3 signal transduction pathways via ligand-independent dimerization and PTK activation. To test this hypothesis, we expressed a series of ETV6-NTRK3 mutants in NIH3T3 cells and assessed their transformation activities. Deletion of the ETV6 HLH domain abolished dimer formation with either ETV6 or ETV6-NTRK3, and cells expressing this mutant protein were morphologically non-transformed and failed to grow in soft agar. An ATP-binding mutant failed to autophosphorylate and completely lacked transformation activity. Mutants of the three NTRK3 PTK activationloop tyrosines had variable PTK activity but had limited to absent transformation activity. Of a series of signaling molecules well known to bind to wild-type NTRK3, only phospholipase-Cg (PLCg) associated with ETV6-NTRK3. However, a PTK active mutant unable to bind PLCg did not show defects in transformation activity. Our studies con®rm that ETV6-NTRK3 is a transforming protein that requires both an intact dimerization domain and a functional PTK domain for transformation activity. Oncogene (2000) 19, 906 ± 915.

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