PTEN loss in the continuum of common cancers, rare syndromes and mouse models

M. Christine Hollander, Gideon M. Blumenthal, Phillip A. Dennis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)289-301
Number of pages13
JournalNature Reviews Cancer
Volume11
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Multiple Hamartoma Syndrome
Germ-Line Mutation
Neoplasms
Lipids
Phosphoprotein Phosphatases
Endometrial Neoplasms
Tumor Suppressor Genes
Phosphatidylinositol 3-Kinases
Thyroid Neoplasms
Phosphoric Monoester Hydrolases
Carcinogenesis
Breast Neoplasms
Phenotype
Mutation
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

PTEN loss in the continuum of common cancers, rare syndromes and mouse models. / Hollander, M. Christine; Blumenthal, Gideon M.; Dennis, Phillip A.

In: Nature Reviews Cancer, Vol. 11, No. 4, 04.2011, p. 289-301.

Research output: Contribution to journalArticle

Hollander, M. Christine ; Blumenthal, Gideon M. ; Dennis, Phillip A. / PTEN loss in the continuum of common cancers, rare syndromes and mouse models. In: Nature Reviews Cancer. 2011 ; Vol. 11, No. 4. pp. 289-301.
@article{36c84a58920b49f3b7429f1c58ff3d55,
title = "PTEN loss in the continuum of common cancers, rare syndromes and mouse models",
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.",
author = "Hollander, {M. Christine} and Blumenthal, {Gideon M.} and Dennis, {Phillip A.}",
year = "2011",
month = "4",
doi = "10.1038/nrc3037",
language = "English (US)",
volume = "11",
pages = "289--301",
journal = "Nature Reviews Cancer",
issn = "1474-175X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - PTEN loss in the continuum of common cancers, rare syndromes and mouse models

AU - Hollander, M. Christine

AU - Blumenthal, Gideon M.

AU - Dennis, Phillip A.

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953038262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953038262&partnerID=8YFLogxK

U2 - 10.1038/nrc3037

DO - 10.1038/nrc3037

M3 - Article

C2 - 21430697

AN - SCOPUS:79953038262

VL - 11

SP - 289

EP - 301

JO - Nature Reviews Cancer

JF - Nature Reviews Cancer

SN - 1474-175X

IS - 4

ER -