PTEN loss in the continuum of common cancers, rare syndromes and mouse models
By M. Hollander, Gideon M. Blumenthal, Phillip A. Dennis. Nature Reviews. Cancer, 2011
805 citations recorded by the source corpus.
PTEN is among the most frequently inactivated tumour suppressor genes in sporadic cancer. PTEN has dual protein and lipid phosphatase activity, and its tumour suppressor activity is dependent on its lipid phosphatase activity, which negatively regulates the PI3K–AKT–mTOR pathway. Germline mutations in PTEN have been described in a variety of rare syndromes that are collectively known as the PTEN hamartoma tumour syndromes (PHTS). Cowden syndrome is the best-described syndrome within PHTS, with approximately 80% of patients having germline PTEN mutations. Patients with Cowden syndrome have an increased incidence of cancers of the breast, thyroid and endometrium, which correspond to sporadic tumour types that commonly exhibit somatic PTEN inactivation. Pten deletion in mice leads to Cowden syndrome-like phenotypes, and tissue-specific Pten deletion has provided clues to the role of PTEN mutation and loss in specific tumour types. Studying PTEN in the continuum of rare syndromes, common cancers and mouse models provides insight into the role of PTEN in tumorigenesis and will inform targeted drug development.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/522797530ac6770ef2538e909625ebeb1795f683
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Citations in the corpus
- Multiplex Assessment of Protein Variant Abundance by Massively Parallel Sequencing (2018, background): “41 of the 216 PTEN missense variants are annotated as pathogenic, 25 of which had abundance scores.”
- PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway? (2022, background): “Germline PTEN mutations are found in approximately 80% of patients with the cancer predisposition syndrome Cowden, which is associatedwith ahigh incidenceof breast and thyroid cancer events (45, 46).”
- Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “Since Cowden disease is one of the cancer predisposition syndromes (641), these studies showed that the tumor suppressive function of PTEN is primarily associated with its lipid phosphatase activity.”
- Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs (2011, positive): “…on the ceRNA network encompassing PTEN, a critical tumor suppressor gene that encodes a phosphatase that converts phosphatidylinositol 3,4,5-trisphosphate to phosphatidylinositol 4,5-bisphosphate, thereby antagonizing the highly oncogenic PI3K/Akt-signaling pathway (Hollander et al., 2011).”
- Dysregulation of AKT Pathway by SMYD2-Mediated Lysine Methylation on PTEN (2015, background): “Genetic alteration of PTEN, including somatic mutations and deletion, and/or epigenetic silencing are frequently observed in various types of cancer [36].”