Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sporadic prostate carcinoma is the most common male cancer in the Western world, yet many of the major genetic events involved in the progression of this often fatal cancer remain to be elucidated. Numerous cytogenetic and allelotype studies have reported frequent loss of heterozygosity on chromosomal arm 10q in sporadic prostate cancer. Deletion mapping studies have unambiguously identified a region of chromosome 10q23 to be the minimal area of loss. A new tumor suppressor gene, PTEN/MMAC1, was isolated recently at this region of chromosome 10q23 and found to be inactivated by mutation in three prostate cancer cell lines. We screened 80 prostate tumors by microsatellite analysis and found chromosome 10q23 to be deleted in 23 cases. We then proceeded with sequence analysis of the entire PTEN/MMAC1 coding region and tested for homozygous deletion with new intragenic markers in these 23 cases with 10q23 loss of heterozygosity. The identification of the second mutational event in 10 (43%) tumors establishes PTEN/MMAC1 as a main inactivation target of 10q loss in sporadic prostate cancer.
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PMID:Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. 937 90

The long arm of chromosome 10 is frequently affected by allelic loss in prostate cancer. PTEN/MMAC1, a candidate tumor suppressor gene located at 10q23.3, a region commonly deleted in prostate cancer, was recently identified and found to be deleted or mutated in cancer cell lines derived from a variety of human tissues including prostate. To examine the role of PTEN/MMAC1 in the progression of prostate cancer, we screened a unique set of 50 metastatic prostate cancer tissues from 19 cancer-death patients for alterations in the PTEN/MMAC1 gene, using single-strand conformational polymorphism analysis and direct sequencing to identify sequence changes and microsatellite analysis to examine allelic loss in the vicinity of PTEN/MMAC1. Overall, gene alterations (deletions or point mutations) were observed in at least 1 metastatic site in 12 of the 19 patients studied. Two cases had homozygous deletions that were confirmed by fluorescence in situ hybridization analysis. Four patients harbored point mutations, with one mutation being found in all four tumors (a primary lesion and three different metastases) from the same patient. The remaining three mutations were detected in only one of multiple metastases. Loss of heterozygosity was found in 10 of 18 informative cases, with 1 case showing a unique pattern of microsatellite instability in each of six different metastases examined. Loss of the same allele was found in all metastases in a given patient in 9 of 10 cases. These results indicate that PTEN/MMAC1 gene alterations occur frequently in lethal prostate cancer, although a substantial amount of mutational heterogeneity is found among different metastatic sites within the same patient. These latter findings emphasize the potentially complex genetic relationship that can exist between various clonal lineages of prostate cancer cells as they evolve during the metastatic process and suggest a molecular basis for phenotypic heterogeneity of different prostate cancer foci in patients with disseminated disease.
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PMID:Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. 944 92

PTEN/MMAC1 is a candidate tumor suppressor gene recently identified at chromosomal band 10q23. It is mutated in sporadic brain, breast, and prostate cancer and in the germ line of patients with hereditary Cowden disease. We searched for genetic alterations of the PTEN/MMAC1 gene in 39 primary head and neck cancers (HNSCCs), 42 primary non-small cell lung cancers (NSCLCs), 80 pancreatic cancer xenografts, and 37 cell lines and xenografts from colon, lung, and gastric cancers. Microsatellite analysis revealed loss of heterozygosity at markers near the gene in 41% of primary HNSCCs, 50% of NSCLCs, and 39% of the pancreatic cancers. Three cases of HNSCCs displayed homozygous deletion involving the gene. We sequenced the entire coding region of the PTEN/MMAC1 gene in the remaining tumors displaying loss of heterozygosity and found one terminating mutation in a HNSCC sample. Thus, a second inactivation event was observed in 4 of 39 primary HNSCC cases. By use of a protein truncation assay, one terminating mutation was also identified in one of eight NSCLC cell lines. Our results suggest that PTEN/MMAC1 gene inactivation plays a role in the genesis of some tumor types.
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PMID:Analysis of PTEN/MMAC1 alterations in aerodigestive tract tumors. 945 98

Cowden disease, a dominantly inherited syndrome characterized by a variety of proliferative lesions and predisposition to breast and thyroid cancer, has recently been linked to the polymorphic marker D10S215 on chromosome segment 10q23. Loss of heterozygosity in prostate cancer is linked to the same marker, whereas loss of heterozygosity in glioblastoma, endometrial cancer, and other malignancies also localizes to this region. Most recently, a putative tumor suppressor gene (PTEN/MMAC1) has been identified in the region between D10S215 and an adjacent, more telomeric marker (D10S541) and was found to be altered in breast cancers, prostate cancers, and glioblastomas. We examined 22 invasive breast cancers for loss of heterozygosity in the 10q23 region and found loss in 41% (9/22). There were two distinct regions of loss, including one near the D10S541 marker, with an approximately equal frequency of deletion in each. The observed pattern of deletion is consistent with the presence of a tumor suppressor gene between D10S215 and D10S541. Most of the poorly differentiated carcinomas in the case collection showed loss of heterozygosity in the region near D10S215, suggesting that this loss correlates with a poor prognosis.
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PMID:Sporadic breast cancers exhibit loss of heterozygosity on chromosome segment 10q23 close to the Cowden disease locus. 949 29

The recently identified PTEN/MMAC1 gene is a candidate tumor suppressor implicated in multiple tumor types based on mutations or homozygous deletions of the gene in certain human cancers. No studies of PTEN/MMAC1 mRNA or protein expression in cancer cells have been reported, primarily because of significant numbers of normal cells contaminating most tumor samples and because of the lack of antibody reagents. We examined PTEN/MMAC1 in advanced prostate cancer for gene mutations or abnormalities in expression by using a series of recently derived xenografts free of normal human cells and a PTEN/MMAC1-specific antibody. Only 1 of 10 tumors contained a homozygous deletion of PTEN/MMAC1, and no mutations were detected in the entire coding region of the remaining nine xenografts. However, five of these showed reduced or absent PTEN/MMAC1 expression by Northern analysis and reverse transcription-PCR of mRNA. PTEN/MMAC1 mRNA expression was restored in nonexpressing prostate cancer cells by in vitro treatment with the demethylating agent 5-azadeoxycytidine. Alterations in PTEN/MMAC1 expression were confirmed at the protein level by immunoblot analysis, and immunohistochemical studies show that the endogenous wild-type PTEN/MMAC1 protein is localized exclusively in the cytoplasm. These results demonstrate that loss of PTEN/MMAC1 expression occurs frequently in advanced prostate cancer.
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PMID:Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. 956 Feb 61

Loss of chromosome 10q is a frequently observed genetic defect in prostate cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identified and mapped to chromosome 10q23.3. We studied PTEN structure and expression in 4 in vitro cell lines and 11 in vivo xenografts derived from six primary and nine metastatic human prostate cancers. DNA samples were allelotyped for eight polymorphic markers within and surrounding the PTEN gene. Additionally, the nine PTEN exons were tested for deletions. In five samples (PC3, PC133, PCEW, PC295, and PC324), homozygous deletions of the PTEN gene or parts of the gene were detected. PC295 contained a small homozygous deletion encompassing PTEN exon 5. In two DNAs (PC82 and PC346), nonsense mutations were found, and in two (LNCaP and PC374), frame-shift mutations were found. Missense mutations were not detected. PTEN mRNA expression was clearly observed in all cell lines and xenografts without large homozygous deletions, showing that PTEN down-regulation is not an important mechanism of PTEN inactivation. The high frequency (60%) of PTEN mutations and deletions indicates a significant role of this tumor suppressor gene in the pathogenesis of prostate cancer.
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PMID:Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. 966 80

The PTEN/MMAC1/TEP1 gene, located at 10q23.3, is a tumor suppressor gene responsible for the familial cancer syndromes Cowden disease and Bannayan-Zonana syndrome, and is commonly somatically mutated in several types of cancers. Mutations of the PTEN gene have been found in prostate cancer cell lines and LOH at 10q22-24 in prostate tumors have also been described with a high frequency. To determine the role of this gene in prostate tumorigenesis, we therefore analysed 22 primary tumors for loss of heterozygosity (LOH) within the 10q22-23 region such that tumors hemizygous at those loci may be examined for somatic PTEN mutations. Losses of heterozygosity of at least one locus was found in 12 (55%) of the 22 tumors DNAs. Among these, six tumors exhibited allele loss in the interval between D10S1765 and D10S541 wherein lies the PTEN gene. We searched the entire coding region of PTEN for somatic mutations in these six tumors. One somatic mutation (17%), a 1 bp deletion, was detected in exon 7 of the gene, in one tumor, indicating that somatic mutations of the PTEN gene may occur in primary prostate tumors.
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PMID:PTEN/MMAC1/TEP1 involvement in primary prostate cancers. 967 8

The PTEN/MMAC1 gene at 10q23.3, which has dual specific phosphatase activity, is a novel tumor suppressor gene candidate. Various kinds of tumors have mutations in this gene, including glioblastoma, endometrial carcinoma and prostate cancer. We examined 29 cases of primary non-Hodgkin's lymphoma (NHL) for mutations in the PTEN/MMAC1 gene. One case of diffuse large B cell lymphoma had an 11 bp deletion, but the remaining 28 cases showed no mutations in the genome. Two of these 28 cases showed missense mutations in the PTEN/MMAC1 transcripts, but no alterations in the genomic DNA. These mRNA missense variants are similar to PTEN/MMAC1 transcript aberrations which have been reported in patients with breast cancer. These findings suggest that alterations in the PTEN/MMAC1 gene play a role in the pathogenesis of NHL.
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PMID:Mutational analysis of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma. 969 84

Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located on chromosome 10q23.3 has been implicated as a new tumor suppressor gene in human cancer. Allelic loss and mutation of this gene has been reported in epithelial derived tumors, including breast cancer and prostate cancer, and in glioblastoma multiforme. The present study was designed to evaluate the potential involvement of PTEN in the pathogenesis of lymphoid neoplasms. We analyzed 27 hematopoietic cell lines (representing a variety of lymphoid lineages), 65 primary lymphoid tumors (including 24 lymphoblastic leukemia/lymphoma [LBL], 30 large B-cell lymphoma [LBCL], 7 Burkitt's lymphoma [BL], and 4 anaplastic large cell lymphoma [ALCL]), and 25 nonmalignant lymph node controls. Gene deletion and gross rearrangement were evaluated using Southern blot analysis, and mutations were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) (PCR-SSCP) and sequencing. Six of 27 cell lines (22.2%) and 3 of 65 primary lymphomas (4.6%) contained alterations of this gene. A large homozygous deletion spanning exons 2 through 5 was detected in one LBL cell line, and two insertions potentially resulting in premature termination, were detected in a second LBL cell line. Nonconservative nucleotide variations were found in two other cell lines (one LBCL and one BL) and in one primary case of LBCL. In addition, two other cell lines (one BL and one myeloma) and two primary lymphomas, both LBCL, contained small deletions within intron 7. These deletions mapped to a poly-T-rich tract just 5' to the intron 7/exon 8 spice site. Their significance is unclear, as they may represent polymorphisms. Overall, our results suggest that abnormalities of the PTEN gene can contribute to pathogenesis in a small percentage of malignant lymphomas.
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PMID:PTEN gene alterations in lymphoid neoplasms. 978 81

Deletion of the q23-24 region of human chromosome 10 is one of the most frequent genetic alterations in prostate cancer, suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. A candidate gene, PTEN/MMAC1, has been identified from this chromosomal region; mutations of this gene have been found in various advanced tumors and cell lines including those of prostate cancer. To further define the role of PTEN/MMAC1 in the development of prostate cancer and its spectrum of genetic alterations, we analysed 40 pT2 or pT3 prostate tumors for allelic loss, mutations, and homozygous deletions using PCR-based methods. Six tumors showed loss of heterozygosity for one of the ten markers analysed, while one tumor showed loss of two markers. None of the markers within PTEN/MMAC1 was lost. Direct sequencing of PCR amplified exons and intron/exon junctions of all 40 tumors revealed three sequence variants, one of which was a point mutation in exon 9, while the other two were polymorphisms. Using multiplex PCR, no homozygous deletions were detected in any of the neoplasms. Our results showing a low frequency of alterations of PTEN/MMAC1 in pT2 and pT3 prostate cancers suggest that this gene plays an insignificant role in the development of most low stage carcinomas of the prostate.
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PMID:PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate. 978 41


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