Global child health priorities: what role for paediatric oncologists?

Despite increasing globalisation, international mobility and economic interdependence, 9.7 million children aged less than 5 years in low income countries will die this year, almost all from preventable or treatable diseases. Diarrhoea, pneumonia and malaria account for 5 million of these deaths each year, compared to about 150,000 deaths from childhood cancer in low- and middle-income countries. In high-income countries, 80% of the 50,000 children diagnosed with cancer each year survive, yet cancer remains the leading disease-related cause of childhood death. In low- and middle-income countries, where 80% of children live, the 200,000 children diagnosed with cancer each year have limited access to curative treatment, and only about 25% survive. Some might argue that death from paediatric cancer in poor countries is insignificant compared to death from other causes, and that scarce health resources may be better used in other areas of public health. Is there a role for the treatment of children with cancer in these regions? Do international partnerships or 'twinning' programmes enhance local health care or detract from other public health priorities? What is ethical and what is possible? This review examines the health challenges faced by infants and children in low-income countries, and assesses the role and impact of international paediatric oncology collaboration to improve childhood cancer care worldwide.

Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations.

PURPOSE: Traditional genetic approaches to identify gene mutations in cancer are expensive and laborious. Nonetheless, if we are to avoid rejecting effective molecular targeted therapies, we must test these drugs in patients whose tumors harbor mutations in the drug target. We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities. MATERIALS AND METHODS: Gene expression profiles of 46 samples of medulloblastoma were generated using the U133av2 Affymetrix oligonucleotide array and validated using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Genetic abnormalities were confirmed using fluorescence in situ hybridization (FISH) and direct sequencing. RESULTS: Unsupervised analysis of gene expression profiles partitioned medulloblastomas into five distinct subgroups (subgroups A to E). Gene expression signatures that distinguished these subgroups predicted the presence of key molecular alterations that we subsequently confirmed by gene sequence analysis and FISH. Subgroup-specific abnormalities included mutations in the Wingless (WNT) pathway and deletion of chromosome 6 (subgroup B) and mutations in the Sonic Hedgehog (SHH) pathway (subgroup D). Real-time RT-PCR analysis of gene expression profiles was then used to predict accurately the presence of mutations in the WNT and SHH pathways in a separate group of 31 medulloblastomas. CONCLUSION: Genome-wide expression profiles can partition large tumor cohorts into subgroups that are enriched for specific genetic alterations. This approach may assist ultimately in the selection of patients for future clinical trials of molecular targeted therapies.