Our results suggest that mutation of the PTEN/MMAC1 gene does not play a major role in carcinogenesis, at least in the tumor types from Japanese patients analyzed in this study.
A pathway in endometrial carcinogenesis involving PTEN mutation and microsatellite instability is confirmed, and this study also indicates the importance of PTEN and hMLH1 methylation in this pathway.
Studies examining PTEN and ERG simultaneously found these genes are likely to occur together, but cooperative tumorigenesis functions have not been conclusively established.
The PTEN mutations have significant effect on the expression silencing of PTEN protein indicating the important role of PTEN mutation in carcinogenesis of breast cancers.
Further studies will disclose a better understanding of the role of mutation in the PTEN gene in the course of tumorigenesis of both benign and malignant tumors developed in patients with CD.
Genes most commonly associated with the process of oncogenesis include: p53 inactivating mutation; hDM2 overexpression; p16 reduced expression; K-/H-RAS activating mutation; PTEN inactivating mutation/deletion; EGFR activating mutation and overexpression; retinoblastoma inactivating mutation and deletion; Cyclin proteins overexpression; CD95 reduced expression; protective BCL-2 proteins overexpression; to name but just a few of such molecules.
These results indicate that PTEN is a constitutive protein in the endometrium, so that the somatic mutation of PTEN exerts a crucial effect on the endometrial carcinogenesis.
Our data, thus, reveal a novel mechanism of tumorigenesis in patients with germline or somatic mutations affecting PTEN ATP-binding motifs, i.e. qualitative and quantitative impairment of PTEN due to the loss of its phosphatase activity, and nuclear mislocalization, resulting in rapid PTEN protein degradation, suppression of p53-mediated transcriptional activity, loss of protection against oxidative stress as well as accumulation of spontaneous DNA DSBs.
In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently inactivated in human prostate cancer.
However, somatic mutations of PTEN may not play a major role in tumorigenesis, at least in colorectal cancers, esophageal papillomas and gingival papillomas.
In summary, our data suggest a novel mechanism whereby SDHD germline variants SDHD-G12S or SDHD-H50R induce thyroid tumorigenesis mediated by PTEN accumulation in the nucleus and may shed light on potential treatment with SRC inhibitors like bosutinib in PTEN-wild-type SDHD-variant/mutation positive CS/CSL patients and sporadic thyroid neoplasias.
These data indicate that point mutations in the PTEN/MMAC1 gene are probably not an important factor in tumorigenesis and the progression of a major subset of lung cancers.
The development of carcinogenesis in the CLC and HCC-like areas in this case might differ, following a common PTEN mutation, although alteration of the kinase-RAS module is the most common molecular event in CLC.
The purpose of this study was to investigate whether p53 and PTEN mutations play a role in the carcinogenesis of STS, as well as to evaluate their mutual role in STS pathogenesis.
Intriguingly, five CPGs showed concordance between CNL and down-regulation in 50 or more tumor samples: MTAP (216 samples), PTEN (143), MCPH1 (86), SMAD4 (63), and MINPP1 (51), which may represent the recurrent driving force for gene expression change during oncogenesis.
In this study, we explored the possibility that PTEN alteration may cause carcinogenesis of endometrioid carcinoma by regulating the expression of the NDRG1 gene.
Recent novel and promising findings include additional abnormalities in key pathways associated with thyroid tumorigenesis (RET-Ras-BRAF-MEK; RET-beta-cateinin; TRK-PI3K-AKT; and MDM-p53-PTEN), single-nucleotide polymorphisms associated with thyroid cancer susceptibility, epigenetic silencing, alternative splicing, and gene expression abnormalities.
We also discuss the significance of this altered regulation in tumor models of PTEN deletion, as well as the potential implications of the unique p110β regulation on GPCR-driven tumorigenesis.
Furthermore, PIK3CA amplification was predominantly detected in tumors with no PTEN alterations, suggesting that mutations of PTEN and PIK3CA are mutually exclusive events in gastric tumorigenesis.
The tumors were sequenced for mutations in the TERT promoter and 22 additional cancer-related genes, interestingly; one patient was shown to carry a deleterious intronic variant in PTEN, a tumor suppressor gene coupled to thyroid tumorigenesis and Cowden syndrome.
Our results suggest either that mutation of PTEN is a late event in prostate tumorigenesis, or that another tumour suppressor gene important in prostate cancer may lie close to PTEN in 10q23.