PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Approximately 20-30% of colorectal carcinomas involve biallelic inactivation of PTEN through a combination of genetic and epigenetic mechanisms. The R15I missense mutation falls within the PIP2 binding motif in the phosphatase domain of PTEN, which involves residues 6-15. PTEN R15I has been show to result in loss of phosphatase activity in vitro. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with loss of heterozygosity (LOH) may also occur. PTEN mutations may occur in multiple exons. Somatic mutations in PTEN have been found in 4--8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. This particular variant is likely to be oncogenic. In preclinical studies, PTEN loss is associated with decreased sensitivity of EGFR mutant lung tumors to EGFR TKIs. Clinical trials assessing the efficacy of PI3K inhibitors in PTEN loss are being explored.

PTEN is a tumor suppressor gene, located on chromosome 10q23. It encodes a lipid and protein phosphatase that negatively regulates the PI3K/AKT/mTOR pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome while somatic mutations are also known to occur in multiple malignancies. PTEN p.Y68H is a reported pathogenic variant that causes tyrosine to histidine substitution at codon 68 affecting NH2-terminal phosphatase domain. This variant has been reported previously in association with PTEN-related disorders. Functional studies demonstrate that individuals harboring this variant have decreased levels of the PTEN protein when compared to wild type controls. However, its clinical significance remains to be fully elucidated.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Most PTEN mutations are loss-of-function mutations. Mono-allelic or bi-allelic loss of PTEN is found in a considerable fraction of tumors, including gliomas (75%). In glioblastoma, PTEN loss/deletion is associated with poor patient prognosis, and/or shorter disease-free survival. The PTEN P169H mutation, however, is not definitively known to cause a loss-of-function change in the PTEN protein and has been shown to confer a phosphatase activity similar to wild-type PTEN in yeast. This variant has been identified in one case of glioblastoma according to the literature. This result should be interpreted in the clinicopathologic context.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in 15% of anaplastic thyroid cancer. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. Patients with Cowden syndrome have an increased risk of developing epithelial thyroid cancer, follicular carcinoma being the most common, of up to 10% compared to <1% in the general population. The PTEN I101T has been observed in a variety of cancer types. One study identified the PTEN I101T variant in 1 out of 172 patients with germ line PTEN mutations. Of note, an in vitro studied observed that the PTEN I101T variant reduced the half-life of PTEN as well as significantly reduced its activity. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

PTEN is a lipid and protein phosphatase that negatively regulates the PI3K/AKT/mTOR pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in ~2% of head and neck squamous cell carcinomas and 15% of anaplastic thyroid carcinomas. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. This particular variant M134I has been reported as a likely pathogenic germline variant (ClinVar, https://preview.ncbi.nlm.nih.gov/clinvar/variation/428267/) and has also been reported as a somatic variant. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. PTEN mutations are loss-of-function mutations and occur in 3% of urothelial carcinomas. The above variants (R130Q and G165R) are predicted to result in loss of function based on preclinical in vitro studies. Whether PTEN alterations predict for responsiveness to mTORC1 inhibitors is less certain at this time.

PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with loss of heterozygosity (LOH) may also occur. PTEN mutations may occur in multiple exons. Somatic mutations in PTEN have been found in 4--8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. In preclinical studies, PTEN loss is associated with decreased sensitivity of EGFR mutant lung tumors to EGFR TKIs. Clinical trials assessing the efficacy of PI3K inhibitors in PTEN loss are being explored. This particular variant is known to be oncogenic. It has also been reported as pathogenic/likely pathogenic germline variant according to ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/376032/).

PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with loss of heterozygosity (LOH) may also occur. PTEN mutations may occur in multiple exons. Somatic mutations in PTEN have been found in 4--8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. In preclinical studies, PTEN loss is associated with decreased sensitivity of EGFR mutant lung tumors to EGFR TKIs. Clinical trials assessing the efficacy of PI3K inhibitors in PTEN loss are being explored. This particular variant is known to be oncogenic.

PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with loss of heterozygosity (LOH) may also occur. PTEN mutations may occur in multiple exons. Somatic mutations in PTEN have been found in 4-8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. In preclinical studies, PTEN loss is associated with decreased sensitivity of EGFR mutant lung tumors to EGFR TKIs. Clinical trials assessing the efficacy of PI3K inhibitors in PTEN loss are being explored. The PTENI101T has been observed in a variety of cancer types, most frequently gliomas, and has been predicted to be pathogenic. However, one study identified the PTEN I101T variant in 1 out of 172 patients with germline PTEN mutations.

PTEN is a lipid and protein phosphatase that negatively regulates the PI3K/AKT/mTOR pathway. PTEN has been reported to show nonsense and frameshift mutations in approximately 10% of adult T cell ALL patients. PTEN mutations may occur together with large deletions of PTEN which are not detected by this assay. PTEN abnormalities are thought to be more frequent in NOTCH1/FBXW7 unmutated T-ALL and appear to be mutually exclusive of NRAS/KRAS mutations in T-ALL. PTEN alterations are associated with reduced or absent protein expression and may be associated with a poor prognosis in adult T cell ALL, but not pediatric T-ALL, according to some studies. PTEN alterations appear to be infrequent among myeloid malignancies.

PTEN mutations occur in 5-14% of colorectal cancers. PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. PTEN loss of expression is observed with KRAS, BRAF, and PIK3CA mutations. In retrospective studies, PTEN loss is associated with decreased sensitivity of colorectal cancer tumors to anti-EGFR antibodies. PTEN loss is associated with lack of benefit of the anti-EGFR antibody, cetuximab.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in 15% of anaplastic thyroid cancer. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. Patients with Cowden syndrome have an increased risk of developing epithelial thyroid cancer, follicular carcinoma being the most common, of up to 10% compared to <1% in the general population. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

Somatic mutations in PTEN have been found in 4-8% of non-small cell carcinomas (NSCLC) including adenocarcinomas and squamous cell carcinomas. PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN is most commonly due to promoter hypermethylation, while homozygous deletion and nonsense mutations with loss of heterozygosity (LOH) may also occur. PTEN mutations may occur in multiple exons. In preclinical studies, PTEN loss is associated with decreased sensitivity of EGFR mutant lung tumors to EGFR TKIs. Clinical trials assessing the efficacy of PI3K inhibitors in PTEN loss are being explored.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. PTEN mutations are loss-of-function mutations and occur in 1% to 5% of ccRCCs. Recent studies suggest that only biallelic loss, resulting from deletion and/or inactivating mutations, is associated with an adverse outcome in ccRCCs. Whether PTEN alterations predict for responsiveness to mTORC1 inhibitors is less certain at this time.

PTEN is a tumor suppressor gene, located on chromosome 10q23, and loss of PTEN results in upregulation of the PI3K/ AKT pathway. Loss of PTEN may occur due to homozygous deletion, nonsense mutations, promoter hypermethylation, or with loss of heterozygosity (LOH). In prostate cancer, homozygous deletions spanning the PTEN locus occurs at one of the highest rates of any tumor type studied thus far. PTEN mutations may occur in multiple exons. Approximately in 25%-70% of prostate cancer, PI3K pathway has been altered either through PI3k overactivation or PTEN inactivation. PTEN is inactivated mainly through deletion in nearly 40%, or mutations in about 10%; both are more common in advanced prostate cancer.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Most PTEN mutations are loss-of-function mutations. Mono-allelic or bi-allelic loss of PTEN is found in a considerable fraction of tumors, including gliomas (75%). In glioblastoma, PTEN loss/deletion is associated with poor patient prognosis, and/or shorter disease-free survival. There are ongoing clinical trials investigating anti-tumor activity of agents in recurrent glioblastoma with this mutation.

PTEN is a tumor suppressor gene, located on chromosome 10q23. It encodes a lipid and protein phosphatase that negatively regulates the PI3K/AKT/mTOR pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome while somatic mutations are also known to occur in multiple malignancies. PTEN alterations are rare and not well characterized in parathyroid tumors. One study reported loss of heterozygosity of PTEN in 7 of 14 parathyroid carcinomas. PTEN p.G165R variant is a reported pathogenic variant that causes glycine to arginine substitution at codon 165 affecting NH2-terminal phosphatase domain. This variant has been reported previously in endometrial and CNS tumors in COSMIC data base. Functional studies demonstrate that individuals harboring this variant have decreased levels of the functional PTEN protein when compared to wild type controls. However, its clinical significance remains to be fully elucidated.

PTEN is a tumor suppressor gene, located on chromosome 10q23. It encodes a lipid and protein phosphatase that negatively regulates the PI3K/AKT/mTOR pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome while somatic mutations are also known to occur in multiple malignancies, particularly as an early event in the development of endometrial cancer. PTEN gene sequence abnormalities are highly variable in type (frameshifts, point mutations) and can occur throughout all 9 exons. Germline mutations of PTEN, found in Cowden’s syndrome, are associated with an increased risk of endometrial cancer. Somatic mutations of PTEN occur in up to 50% of complex atypical hyperplasia and type I endometrial adenocarcinomas. Clinical trials assessing the efficacy of PI3K and mTOR inhibitors in PTEN loss are being explored.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Mono- and bi-allelic loss of PTEN is found in approximately 40-50% and 5% of breast cancers, respectively. It has been reported to occur in BRCA1-associated basal-like breast cancer. Germline mutations in PTEN are also responsible for Cowden disease, a rare autosomal dominant multiple-hamartoma syndrome. In one study, germline mutations of PTEN have been reported to be associated with 85% lifetime risk of breast cancer in patients with PTEN hamartoma tumor syndrome. Aberrant PTEN pathway is associated with metastases and poor prognosis in breast cancer. It also predicts poor response to trastuzumab. There are ongoing clinical trials investigating anti-tumor activity of PI3K-beta inhibitor in PTEN deficient tumors.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. PTEN mutations have been reported in up to 19% of gastric cancers. Germline mutations in PTEN are also responsible for Cowden disease, a rare autosomal dominant multiple-hamartoma syndrome. Patients with Cowden disease can have gastric polyps, but a possible association with gastric cancer needs further study. Inactivation of PTEN is shown to be closely associated with tumor progression and metastases. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. PTEN somatic point mutations are infrequent, but allelic loss or altered expression is seen in approximately 20% and 40% of the melanoma cases, respectively. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.

This gene is a known cancer gene.

This gene is a known cancer gene.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. PIK3CA mutations are present in ~5% of cutaneous melanomas. PIK3CA M1043I is a known oncogenic hotspot mutation. M1043I confers a gain of function on the protein as indicated by in increased activation of downstream signaling and and transformation in cell culture. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways.The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with 80% of the identified mutations found within three hotspot: E542K, E545K, and H1047R. PIK3CA mutations are often found in hormone receptor positive breast cancer and have been associated with resistance to anti-EGFR therapy in some studies but not in others.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains). Activating mutations in PIK3CA are found in a wide variety of human cancers including up to 4% of prostate cancers. The role of PIK3CA mutations as prognosticators of outcome or predictors of therapeutic response awaits further evaluation. Clinical trials are available for patients with PIK3CA mutated tumors.

PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains). Activating mutations in PIK3CA are found in a wide variety of human cancers including up to 5% of renal cell carcinomas. The role of PIK3CA mutations as prognosticators of outcome or predictors of therapeutic response awaits further evaluation. Clinical trials are available for patients with PIK3CA mutated tumors.

Somatic mutations in PIK3CA have been found in 10--30% of colorectal cancers. KRAS, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies in metastatic colorectal cancer. Recent 'molecular pathological epidemiology' (MPE) research has shown that aspirin use may be associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation may be a molecular biomarker that predicts response to aspirin therapy. The R88Q mutation falls within the ABD domain of the p110a catalytic subunit and has been shown to result in gain-of-function in vitro. PIK3CA may be a target of directed therapy in some clinical settings.

PIK3CA is the the p110 catalytic subunit-alpha of phosphatidylinositol 3 kinase. Activating mutations of PIK3CA occur in various types. PIK3CA mutations have been reported in approximately 8% of cases of diffuse large B cell lymphoma and are typically mutually exclusive of PTEN loss in that tumor type. PIK3CA mutations are very rare in chronic lymphocytic leukemia and believed to be absent in acute myeloid leukemia and myelodysplastic syndromes. PIK3CA mutations are potentially targetable in some settings and pathway inhibitors are currently under investigation .