Strand bias mutations

Fig. 4 Percentage of tumor mutations at p53 base pairs with purine on the nontranscribed strand. The strand bias of several types of mutations affecting purines is shown in several common human cancers. A strong strand bias is indicative of a possible perturbation of the transcription-repair complex at an adducted DNA base. CpG transitions show almost equal distribution on both strands. GC to TA transversions show a strong strand bias in most cancers. The strong bias of AT to GC transitions in lung and bladder cancer is a clue to the involvement of carcinogens in the genesis of these mutations.

Breast cancer is one of the types of cancer that frequently arises in Li-Frau-meni syndrome families (Kleihues et al., 1997). The mutations found in Li-Fraumeni patients with breast cancer could be representative of background mutations that arise spontaneously in breast cancer. Comparison with sporadic breast cancer shows that two types of mutations, G to T and G to C transversions, have not been found in breast cancer patients in Li-Fraumeni families and thus could be specific for somatic breast cancer. These transversions represent only 18% of all breast cancer mutations. However, they show a strong strand bias and occur at sites also mutated in lung cancers from smokers (G to T transversions, codons 157,248,249 and 273) or in bladder cancers from smokers and/or dye-exposed workers (G to C transversions, codons 158 and 280). 

In eukaryotes, the existence of compositional biases is unclear and most attempts to detect the replication origins from strand compositional asymmetry have been inconclusive. Several studies have failed to show compositional biases related to replication, and analysis of nucleotide substitutions in the region of the -globin replication origin in primates do not support the existence of mutational bias... 

P. Lopez, and H. Philippe, Composition strand asymmetries in prokaryotic genomes mutational bias and biased gene orientation. C. R. Acad. Sci. HI 324, 201-208 (2001). 

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