On the basis of epidemiological studies,
infection was suggested to play a role in the etiology of human
cancer. While for some
cancers such a role was indeed demonstrated, there is no direct biological support for the role of viral pathogens in the pathogenesis of childhood
leukemia. Using a novel bioinformatic tool that alternates between clustering and standard statistical methods of analysis, we performed a 'double-blind' search of published gene expression data of subjects with different childhood
acute lymphoblastic leukemia (ALL) subtypes, looking for unanticipated partitions of patients, induced by unexpected groups of genes with correlated expression. We discovered a group of about 30 genes, related to the
interferon response pathway, whose expression levels divide the ALL samples into two subgroups; high in 50, low in 285 patients. Leukemic subclasses prevalent in early childhood (the age most susceptible to
infection) are over-represented in the high-expression subgroup. Similar partitions, induced by the same genes, were found also in breast and
ovarian cancer but not in
lung cancer,
prostate cancer and
lymphoma. About 40% of
breast cancer samples expressed the '
interferon-related' signature. It is of interest that several studies demonstrated mouse mammary tumor virus-like sequences in about 40% of
breast cancer samples. Our discovery of an unanticipated strong signature of an
interferon-induced pathway provides molecular support for a role for either
inflammation or
viral infection in the pathogenesis of childhood
leukemia as well as breast and
ovarian cancer.