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Background   Alu  elements are the most abundant retrotransposable elements comprising ~11% of the human genome. Many studies have highlighted the role that  Alu  elements have in genetic instability and how their contribution to the assortment of mutagenic events can lead to cancer. As of yet, little has been done to quantitatively assess the association between  Alu  distribution and genes that are causally implicated in oncogenesis.    Results  We have investigated the effect of various  Alu  densities on the mutation type based classifications of cancer genes. In order to establish the direct relationship between  Alu s and the cancer genes of interest, genome wide  Alu -related densities were measured using genes rather than the sliding windows of fixed length as the units. Several novel genomic features, such as the density of the adjacent  Alu  pairs and the number of  Alu -Exon- Alu  triplets, were developed in order to extend the investigation via the multivariate statistical analysis toward more advanced biological insight. In addition, we characterized the genome-wide intron  Alu  distribution with a mixture model that distinguished genes containing  Alu  elements from those with no  Alus , and evaluated the gene-level effect of the 5'-TTAAAA motif associated with  Alu  insertion sites using a two-step regression analysis method.    Conclusions  The study resulted in several novel findings worthy of further investigation. They include: (1) Recessive cancer genes (tumor suppressor genes) are enriched with  Alu  elements (p < 0.01) compared to dominant cancer genes (oncogenes) and the entire set of genes in the human genome; (2)  Alu -related genomic features can be used to cluster cancer genes into biological meaningful groups; (3) The retention of exon  Alus  has been restricted in the human genome development, and an upper limit to the chromosome-level exon  Alu  densities is suggested by the distribution profile; (4) For the genes with at least one intron  Alu  repeat in individual chromosomes, the intron  Alu  densities can be well fitted by a Gamma distribution; (5) The effect of the 5'-TTAAAA motif on  Alu  densities varies across different chromosomes.

Alu distribution and mutation types of cancer genes