Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer

Cytogenetic aberrations have been reported in 45,000 human neoplasms. Structural balanced rearrangements are associated with distinct tumor subtypes with remarkable specificity and have been essential for identifying genes involved in tumorigenesis(1,2). All balanced rearrangements that have been characterized molecularly act by deregulating a gene in one of the breakpoints or by creating a fusion gene(3-6). Because most recurrent aberrations and rearranged genes have been found in hematological disorders, whereas numerous genomic imbalances have been identified in solid tumors(7,8), it has become generally accepted that there are pathogenetic differences between these neoplasms. We here show that in every tumor type, the numbers of recurrent balanced chromosome abnormalities, fusion genes and genes rearranged as a consequence of balanced aberrations are simply a function of the number of cases with an abnormal karyotype. Hence, there may not be any fundamental tissue-specific differences in the genetic mechanisms by which neoplasia is initiated.