Chromosome 10 alterations in prostate adenocarcinoma (review).
Inactivations of tumor suppressor genes are the most common genetic alterations in prostate adenocarcinoma. Such inactivations are frequently accompanied by loss of portions of the chromosome on which the tumor suppressor gene resides. Loss of portions of both 10p and 10q have been identified in a significant percentage of prostate carcinomas, as well as other malignant neoplasms, and such losses are associated with advanced clinical stage and aggressive behavior in these neoplasms. The PTEN tumor suppressor gene has recently been identified as an important tumor suppressor gene at 10q23. This gene encodes a dual specificity protein phosphatase which interacts with and controls the tyrosine phosphorylation of focal adhesion kinase (FAK), a key regulator of signal transduction via focal adhesions. Such focal adhesions are the site at which integrins cluster following interactions with extracellular matrix ligands and interact with both cytoskeletal proteins and signal transduction molecules to effect key processes such as cell migration, spreading and proliferation. The PTEN gene is inactivated in a significant proportion of prostate carcinomas, particularly metastatic prostate cancers. There is also evidence from studies of loss of heterozygosity that at least one additional tumor suppressor gene for prostate cancer is present on the distal portion of 10q. Similarly, both functional studies and direct analysis of human tumors strongly support the idea that at least one, and possibly two, tumor suppressor genes for prostate cancer are present on 10p. Given that inactivations of tumor suppressor genes on chromosome 10 are associated with advanced clinical stage in prostate cancer these genes are attractive candidates both as prognostic markers and as potential targets for therapeutic intervention.
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
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Ittmann
D000230:Adenocarcinoma / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human