Diagnosis and treatment insights for an unusual childhood Cancer Syndrome An unusual case of a young girl with a colon cancer syndrome caused by recessive mutations in the mismatch repair gene MSH6 is described in the February issue of Nature Clinical Practice Oncology. Individuals with mutations in MSH6 are at an increased risk of developing cancer; however, a childhood cancer syndrome caused by these mutations has only recently been recognized.In this article, Richard Scott and colleagues report how a 13-year-old girl who was treated for a brain tumor and leukemia was subsequently diagnosed with multiple colon cancers and skin lesions, despite an absence of hereditary colon cancer. Recessive mutations in the MSH6 gene were identified in this patient and she was successfully treated with surgery and chemotherapy.This case study broadens the tumor spectrum associated with recessive MSH6 mutations and discusses the implications for treatment in such individuals. Many mismatch repair deficiency syndromes are treated with the drug temozolomide, but preclinical and clinical data show that it can cause resistance and may promote further genetic abnormality. Mutations in MSH6 and other mismatch repair genes should be considered in any child presenting with malignancy and abnormal skin pigmentation. Early diagnosis is important so that genetic testing and screening can be offered to relatives, and could also help avoid ineffective chemotherapeutic agents such as temozolomide.
Author contact:Richard Scott (Institute of Cancer Research, Surrey, UK)Tel: +44 208 7224 455; E-mail: richard.scott@icr.ac.uk Editor contact:Lisa Hutchinson (Editor, Nature Clinical Practice Oncology)Tel: +44 20 7843 4837; Email: l.hutchinson@nature.com