Mutation Hotspots

7 Prenatal diagnosis, carrier detection, and gene dierapy 

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Denissenko MF, Pao A, Tang M, Pfeifer GP. (1996). Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53. Science. 274(5286) 430-32. 

The LI loop winds aroimd the P and y phosphates it is also know as the P loop. Glyl2 is located in the LI loop this amino acid is frequently mutated in oncogenic mutants of Ras protein (mutation hotspot ). 

Schmuiie, C, Vang, A, S-, Beart, R. W., and Jones, R A. (1995). Base CKcision repair of U G mismatches at a mutational hotspot in the p53 gene is more efficient than base excision repair of T G mismatches in extracts of human colon tumors. Cancer Rei. 55,3742-3746. 

Puisieux A, Lhn Sj Groopman J, Ozturk M. Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens. Cancer Res 1991 51 6185-9. 

Rogozin, I.B. and Pavlov, Y.I. (2003) Theoretical analysis of mutation hotspots and their DNA sequence context specificity. Mutat. Res., 544, 65-85. 

Krause, M.K., L.D. Rhodes and R.J. Van Beneden. Cloning of the p53 tumor suppressor gene from the Japanese medaka Oryzias latipes) and evaluation of mutational hotspots in MNNG-exposed fish. Gene 189 101-106, 1997. 

Smith, L. E., Denissenko, M. F., Bennett, W. R, Li, H., Amin, S., Tang, M., and Pfeifer, G. P. (2000). Targeting of lung cancer mutational hotspots by polycyclic aromatic hydrocarbons. J Natl Cancer Inst 92, 803-811. 

Templeton, A. R., et al., Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am J... 

M.S. (2006) Acrolein is a major cigarette-related lung cancer agent preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc. Natl. Acad. Sci. USA, 103, 15404-15409. 

Brash, D.E. and Haseltine, W.A. (1982) UV-induced mutation hotspots occur at DNA damage hotspots. Nature, 298, 189-192. 

Fig. 3A Role of exogenous and endogenous factors in shaping tumor mutation patterns. Mini-hotspots in the p53 coding sequence. Distribution of four mutation types in the coding sequence, GC to AT transitions at CpG (representing 23% of all mutations), GC to TA transversions (15%), GC to CG (8%), and AT to GC (12%). CpG transitions primarily appear as the consequence of an endogenous mutation mechanism and form well-defined mutation hotspots. Because of these major hotspots, the mini-hotspots corresponding to other mutation types are difficult to detect. Only sites that contain more than 1 % of a specific mutation type are shown. Hotspot codons for each mutation type are indicated. Some of the non-CpG hotspots are well-characterized sites of alteration induced by exogenous carcinogens (see Fig. 5).

Hsu 1C, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hotspot in the p53 gene in human hepatocellular... 

A crystal structure of human P450 51 is not yet available but high resolution structure of the soluble Mycobacterium tuberculosis P450 51 is (ref [1495]). Two notable features are a bent I helix and an open conformation of the BC loop. The bacterial structure has been utilized in consideration of mammalian models, and the SRS predictions do not seem to apply well . Further, the mutation hotspots for known azole-resistant... 

Rogozin, I. B., Pavlov, Y. I., Bebenek, K., Matsuda, T., and Kunkel, T. A. (2001). Somatic mutation hotspots correlate with DNA polymerase rj error spectrum. Nat. Immunol. 2, 530-536. 

Hu, W., Z. Feng, J. Eveleigh, G. Iyer, J. Pan et al. 2002. The major lipid peroxidation product, fra w-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. 23 ... 

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