Other highlights of the May 7 JNCI

• Osteosarcoma and RECQL4 Gene Mutations: Rothmund–Thomson syndrome (RTS) is an autosomal recessive disorder associated with an increased predisposition to osteosarcoma. Mutations in the RECQL4 gene, which encodes a RecQ DNA helicase, have been reported in a few patients with RTS. Lisa L. Wang, M.D., of the Baylor College of Medicine, Sharon E. Plon, M.D., Ph.D., of Texas Children's Cancer Center, and their colleagues sequenced the RECQL4 genes of 33 patients with RTS to examine whether a predisposition to developing osteosarcoma was associated with a distinctive pattern of RECQL4 gene mutations.

  They found that 23 patients with RTS, including all 11 of those diagnosed with osteosarcoma, carried at least one of 19 truncating mutations in their RECQL4 genes. The incidence of osteosarcoma was 0.00 per year in patients without such mutations and 0.05 per year in patients with such mutations. The authors conclude that mutations predicted to result in the loss of RECQL4 protein function are associated with risk of osteosarcoma.

  Contact: Lori Williams, Baylor College of Medicine, 713-798-7637, loriw@bcm.tmc.edu.

• Thymidylate Synthase Inhibition and PET Scanning: The thymidylate synthase (TS) enzyme, which catalyzes the biosynthesis of thymidine nucleotides used in DNA synthesis, is an important target for antiproliferative chemotherapy. Cells can compensate for the depletion of thymidine nucleotide pools by taking up extracellular thymidine. Paula Wells and Pat Price, M.D., of the Imperial College School of Medicine, and colleagues investigated whether thymidine salvage kinetics could be measured noninvasively in tumor tissue as an indicator of TS inhibition.

  They scanned patients who had advanced gastrointestinal cancers with carbon-labeled thymidine positron emission tomography (PET); some patients were treated with the TS inhibitor AG337, and some were not. Comparison of scans before and after AG337 treatment showed changes in PET parameters that were consistent with increased tumor thymidine incorporation. The PET results were consistent with conventional pharmacodynamic systemic measures of TS inhibition. The authors conclude that carbon-labeled thymidine PET can be used to measure thymidine salvage kinetics directly and noninvasively in tissues of interest.

  Contact: Richard Hoey, Cancer Research UK, 44-207-061-8308, Richard.hoey@cancer.org.uk.

• Guidelines for the Development of Radiation Modifiers: Radiation modifiers are agents that regulate the responses of tumors and normal tissue to radiation and have traditionally consisted of conventional chemotherapeutic agents. Radiation modifiers that target novel molecules or processes are now being developed. In a commentary, A. Dimitrios Colevas, M.D., of the National Cancer Institute, and colleagues present the consensus statement of the Radiation Modifier Working Group of the National Cancer Institute, which reviewed and evaluated past and current preclinical and clinical approaches to the development of combination drug and radiation anticancer therapies. They provide practical guidelines for selecting evaluation criteria for radiation modifiers--including the types of preclinical data that are needed, the appropriate in vitro and in vivo assays, and the need for clinically relevant exposures--as well as the design and implementation of phase I and II studies of radiation modifiers.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.