Prostate cancer mutations

Singh RP, Agarwal R (2004) A cancer chemopreventive agent silibinin, targets mitogenic and survival signaling in prostate cancer. Mutat Res 555 21-32... 

Genetic Familial prostate cancer is inherited in an autosomal dominant manner. Mutations in p53, Rb, E-cahedrin, a-catenin, androgen receptor, KAII, microsatellite instability, loss of heterozygocity at 1, 2q, 12p, 15q, 16p, and 16q. Candidate prostate cancer gene locus identified on chromosome 1. 

Lysine methyltransferases have been linked in various cases to the pathogenesis of cancer. Examples can be found for KMTs that induce repressive marks as well as for those that lead to an activating methylation pattern. Possible reasons for a disturbed regulation of methylation may result in mutations of enzymes or overexpression in cancer cells. An indication for a therapeutic benefit of potential inhibitors is often derived from siRNA knockdown of the requisite isotype. Mutations of MLLl for example are thought to be responsible for various forms of acute leukemia [63]. Overexpression of EZH2 was linked to breast or prostate cancer [64] and increased levels in human cancers have also been observed for G9a. Increased mRNA levels for... 

Chapters 11 and 31. Since cancers contain multiple mutations, they are complex diseases. However, many specific susceptibility loci are being located, including some for breast cancer (Box 11-D),392 prostate cancer,393 and familial adenomatous polyposis, a hereditary disease leading to colon cancer.388 394 Cancer has long been known to be associated with chromosome instability including deletion and insertion mutations at simple repeat sequences, frame-shift mutations,395 DNA breakage, translocation,396 and losses or gains of whole chromosomes 397... 

W. J. Computational Models for Predicting the Binding Affinities of Ligands for the Wild-type Androgen Receptor and a Mutated Variant Associated with Human Prostate Cancer. Chem. Res. Toxicd. 

Schoenberg MP, Hakimi JM, Wang S, Bova GS, Epstein JI, Fischbeck KH, Isaacs WB, Walsh PC, Barrack ER. Microsatellite mutation (CAG24—>18) in the androgen receptor gene in human prostate cancer. Biochem Biophys Res Commun 1994 198(l) 74-80. 

Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK, Keer HN, Balk SP. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 1995 332(21) 1393—1398. 

Tilley WD, Buchanan G, Hickey TE, Bentel JM. Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res 1996 2(2) 277-285. 

Barrack ER. Androgen receptor mutations in prostate cancer. Mt Sinai J Med 1996 63(5-6) 403-412. 

Calvo A, Gonzalez-Moreno O, Yoon CY, Huh JI, Desai K, Nguyen QT, et al. Prostate cancer and the genomic revolution Advances using microarray analyses. Mutat Res 2005 576(l-2) 66-79. 

Direct immunohistochemical analysis of prostatic tissue has become very popular since the development of AR antibodies. However, a disadvantage of this technique in quantitative analysis is that the intensity of the immunohistochemical stain is dependent on the intactness of the structure of the AR. Therefore, mutations or alterations in the structure may reduce staining intensity (T5). Biochemical and immunohistochemical studies of AR content in relation to grade or stage of disease, as well as prediction of response to endocrine therapy, has been inconsistent. Nearly all primary prostate cancer specimens positively express AR protein, as determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis as well as by immunohistochemical analysis on formalin-fixed, paraffin-embedded primary prostate tissues (D12, H14). In advanced-stage prostate cancer, immunohistochemical techniques has shown that metastases in bone, the... 

Mutations have been found in primary untreated, local and metastatic hormone-refractory prostate cancer as well as in LNCaP cells. However, mutations seem to be more common in advanced and hormone-refractory prostate cancers (C25, E5, L4, N3, S30, S31, Tl, T5). This point is still debated. Transition mutations, where a purine is replaced by a purine or a pyrimidine by a another pyrimidine, seems to be more common in prostate cancer than transversion mutations, where a purine is converted to a pyrimidine or vice versa. It was proposed that this may be due to endogenous carcinogens (HI). 

Kll. Koivisto, P. A., and Rantala, I., Amplification of the androgen receptor gene is associated with P53 mutation in hormone-refractory recurrent prostate cancer. J. Pathol. 187, 237-241 (1999). 

K18. Kubota Y., Shuin, T., Uemura, H., Fujinami, K., Miyoto, H., et at, Tumor suppressor gene p53 mutations in human prostate cancer. Prostate 27, 18-24 (1995). 

N3. Newmark, J. R., Hardy, D. O., Tonb, D. C., Carter, B. S., Epstein, J. I., etal., Androgen receptor gene structure mutations in human prostate cancer. Proc. Natl. Acad. Sci. (USA) 89,6319-6323 (1992). 

Suzuki, H., Akakura, K., Komiya, A., Aida, S., Akimoto, S., and Shimazaki, J., Codon 877 mutation in the androgen receptor gene in advanced prostate cancer relation to antiandrogen withdrawal syndrome. Prostate 29, 153-158 (1996). 

Suzuki, H, Sato, N., Watabe, Y., Masai, M., Seino, S., and Shimazaki, J., Androgen receptor gene mutations in human prostate cancer. J. Steroid Biochem. Mol. Biol. 46, 759—765 (1993). 

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