Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN

Gray, Ian C.; Stewart, Lorna; Phillips, S. M. A.; Hamilton, J.; Gray, Nicola E.; Watson, Graham J.; Spurr, Nigel K.; Snary, David

doi:10.1038/bjc.1998.674

Cited by 149 publications

(131 citation statements)

References 5 publications

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“…In fact, the detection of these mutations required the cloning of PCR products obtained from tumor DNA and the sequencing of individual clones. The failure of three other groups to detect MXI1 mutations may well be due to the fact that DNA analyses were performed on the uncloned PCR-ampli®ed population of molecules (Gray et al, 1995;Kawamata et al, 1996;Kuczyk et al, 1998).…”

Section: Prostate Cancermentioning

confidence: 99%

MYC oncogenes and human neoplastic disease

1999

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c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we ®rst summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite di erent roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in speci®c neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which signi®cant and con®rmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

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Section: Prostate Cancermentioning

confidence: 99%

MYC oncogenes and human neoplastic disease

1999

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“…13,15,[93][94][95] Comprehensive surveys of various human cancers for PTEN deletion or mutation reveal that functional loss of PTEN frequently occurs in a wide spectrum of human cancers (reviewed in Vivanco and Sawyers, 2002 6 ). In prostate cancer, at least three mechanisms have been identified for functional loss of PTEN: chromosome deletion or loss of heterozygosity (LOH), [96][97][98][99][100][101] somatic mutations 95,[99][100][101][102][103] and epigenetic aberrations. 104,105 The majority of human prostate cancer cell lines and xenografts that have been evaluated show inactivation of the PTEN tumor-suppressor gene.…”

Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

Ittmann

Ayala

et al. 2005

Prostate Cancer Prostatic Dis

110

112

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The PI3-K-Akt pathway plays a central role in the development and progression of prostate cancer and other malignancies. We review original studies and summarize relevant sections of previous reviews concerning the relationships between abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We discuss laboratory and clinical data that indicate gene perturbation and dysregulation of PI3-K-Akt pathway is common in prostate cancer and other malignancies. We further discuss the critical role of the PI3-K-Akt pathway in the oncogenic signaling network and provide examples that establish the PI3-K-Akt pathway as a focal point for the future development of informative biomarkers and effective therapies for prostate cancer.

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“…Deletion of this region has been repeatedly demonstrated by cytogenetic examination; for example, deletions were detected in 8 of 89 short-term cultures of prostate carcinomas (Arps et al, 1993;Lundgren et al, 1992). Loss of heterozygosity (LOH) analysis has also shown deletions in the 10q23 ± 25 region, occurring in 20 ± 62% of prostate tumors, especially those that are of advanced stage (Bergerheim et al, 1991;Cunningham et al, 1996;Gray et al, 1995;Lacombe et al,1996;Trybus et al, 1996). In one of these studies, the deletion was de®ned at the 10q23 ± 24 boundary (Gray et al, 1995).…”

Section: Introductionmentioning

confidence: 97%

“…Loss of heterozygosity (LOH) analysis has also shown deletions in the 10q23 ± 25 region, occurring in 20 ± 62% of prostate tumors, especially those that are of advanced stage (Bergerheim et al, 1991;Cunningham et al, 1996;Gray et al, 1995;Lacombe et al,1996;Trybus et al, 1996). In one of these studies, the deletion was de®ned at the 10q23 ± 24 boundary (Gray et al, 1995). Introduction of human chromosome 10 into tumor cells of prostate resulted in the suppression of tumor growth or metastasis; 10q23 was within the region responsible for tumor or metastasis suppression (Murakami et al, 1996;Nihei et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate

et al. 1998

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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 identi®ed 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 de®ne 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 ampli®ed 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 insigni®cant role in the development of most low stage carcinomas of the prostate.

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Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN

Cited by 149 publications

References 5 publications

MYC oncogenes and human neoplastic disease

MYC oncogenes and human neoplastic disease

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate

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