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Published on: July 6, 2017
PTEN loss in the continuum of common cancers, rare syndromes and mouse models
M Christine Hollander1, Gideon M Blumenthal, Phillip A Dennis
1Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Abstract:
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.
Insights
PTEN is a crucial tumor suppressor gene. Its inactivation links rare PTEN hamartoma tumor syndromes (PHTS) and common cancers, offering insights for targeted drug development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- PTEN is a frequently inactivated tumor suppressor gene in sporadic cancers.
- PTEN's tumor suppressor activity relies on its lipid phosphatase function, regulating the PI3K-AKT-mTOR pathway.
- Germline PTEN mutations define PTEN hamartoma tumor syndromes (PHTS), including Cowden syndrome.
Purpose of the Study:
- To explore the role of PTEN in tumorigenesis across rare syndromes, common cancers, and mouse models.
- To understand how PTEN inactivation contributes to cancer development.
- To inform the development of targeted therapies for PTEN-associated cancers.
Main Methods:
- Review of PTEN's dual phosphatase activity and its role in the PI3K-AKT-mTOR pathway.
- Analysis of germline PTEN mutations in PHTS and Cowden syndrome.
- Examination of Pten deletion in mouse models to study tissue-specific roles in tumorigenesis.
Main Results:
- PTEN inactivation is common in sporadic cancers and linked to PHTS, with Cowden syndrome showing high PTEN mutation rates.
- Cowden syndrome patients exhibit increased risks for breast, thyroid, and endometrial cancers, mirroring sporadic PTEN-inactivated tumors.
- Mouse models with Pten deletion mimic PHTS phenotypes, elucidating PTEN's function in specific cancer types.
Conclusions:
- Studying PTEN in diverse contexts (syndromes, cancers, mouse models) provides crucial insights into tumorigenesis.
- Understanding PTEN's multifaceted role is essential for developing effective targeted drug strategies.
- PTEN research bridges the gap between rare genetic syndromes and common malignancies.
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