Mutaciones del gen har y factores pronósticos en cáncer de próstata

Steroids can made their action because of specific receptors called androgen, estrogen progesterone and steroid receptors. These receptors are members of a superfamily of nuclear receptors. AR is a 919 amino-acid protein with 98 Kd. Like others nuclear receptors, AR have 4 domains. Chromosomal mappi...

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Bibliographic Details
Main Author Sanchez Zalabardo, Daniel
Format Dissertation
LanguageSpanish
Published ProQuest Dissertations & Theses 01.01.2003
Subjects
Medicine
Molecular biology
Surgery
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Summary:Steroids can made their action because of specific receptors called androgen, estrogen progesterone and steroid receptors. These receptors are members of a superfamily of nuclear receptors. AR is a 919 amino-acid protein with 98 Kd. Like others nuclear receptors, AR have 4 domains. Chromosomal mapping experiments placed the hAR on the X chromosome (Xq11–13). Exon 1 encoes transactivational domain, exons 2–3 the DNA binding domain, exon 4 the hinge region and exons 4–8 the ligand binding domain. The AR was known to have regions of genetic variability or polymorphism. The first polymorphism was a trinucleotide (CAG) identified in the first exon resulting in a polyglutamide tract in the protein. A second trinucleotide polymorphism in the exon 1 (GGC) encodes a polyglicine tract. Aim of the study. (1) Study of hAR mutations by genomic sequentiation in retropubic prostatectomy specimens. (2) Relationship between hAR mutations with clinical and pathological risk factors. (3) Relationship between hAR mutations with biochemical and clinical progression free survival. Material and methods. Genomic sequentiation of radical retropubic prostatectomy specimens of 67 patients with prostate cancer. Results. HAR mutations were observed in 11 patients (16,4%). Exon 1 was the most frequent mutated exon (5 patients), exon 5 had 2 mutations and exons 4,6,7,8 had 1 mutation each. Most frequent mutation was punctual mutation (10 patients). The mean CAG length was 21–7 (median 22). The mean GGC length was 15 (median 17). Conclusions. (1) R mutations frequence in radial prostatectomy specimens was 16.4%. (2) Most frequent mutation was punctual mutation. (3) The mean CAG length was 21.7 (median 22). (4) The mean GGC length was 15 (median 17). (5) CAG length and GGC length have a inverse relation. (6) CAG length is bigger in salvage hAR than in mutated hAR. (7) Patients with mutated hAR have better Gleason score than patients with salvage hAR.