  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 ALL subtypes, looking for
unanticipated partitions of patients, induced by unexpected groups of genes
with correlated expression. We discovered a group of about thirty 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 interested that
several studies demonstrated MMTV-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.
