Mutations of PTEN in patients with Bannayan-Riley-Ruvalcaba phenotype.

Longy, Michel; Coulon, Valérie; Duboué, B.; David, Albert; Larrègue, M; Eng, Charis; Amati, Patrizia; Kraimps, J. L.; Bottani, Armand; Lacombe, Didier; Bonneau, Dominique

doi:10.1136/jmg.35.11.886

Cited by 83 publications

(40 citation statements)

References 11 publications

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“…However, several studies reported the presentation of thyroid nodules and thyroid cancer in young children with PHTS [Ngeow et al, 2011;Smith et al, 2011]. Another report of a malignancy concerned a case of breast cancer in a BRRS patient (the paternal grandmother of the proband died at the age 53 years of breast cancer and endometrial adenocarcinoma) [Longy et al, 1998]. Furthermore, genotypephenotype analysis within the BRRS group confirmed that breast cancer and fibroadenomas have been found in patients with BRRS, CS, or patients with overlapping features [Marsh et al, 1999].…”

Section: Discussionmentioning

confidence: 78%

“…Somatic PTEN deletions and/or mutations occur with a wide distribution of frequencies in sporadic primary tumors, such as endometrial carcinomas, glioblastoma multiform, prostate cancer, breast cancer, and melanomas [De Vivo et al, 2000]. Germ-line PTEN mutations have been identified in patients suffering from CS [Marsh et al, 1998], BRRS [Longy et al, 1998], and Proteus-like syndrome . However, two additional disease phenotypes may also be associated with germ-line mutation or deletion of the PTEN gene.…”

Section: Discussionmentioning

confidence: 99%

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PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol

Piccione

Fragapane

Antona

et al. 2013

American J of Med Genetics Pt A

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PTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth syndromes associated with germ‐line mutations in the tumor suppressor PTEN gene located on 10q23.3. It is widely accepted that two of these disorders, Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome, are allelic conditions. Because PTEN mutations are not identifiable in every case of the PHTS phenotype, the inability to detect a mutation within the PTEN gene does not invalidate the clinical diagnosis of Cowden syndrome, or Bannayan–Riley–Ruvalcaba syndrome, in patients who meet diagnostic criteria for these disorders. PTEN mutations are associated with an increased risk for developing breast, thyroid, endometrial, and sometimes renal cancers. Thus, cancer surveillance is the cornerstone of PHTS patient management. Although a consensus cancer surveillance protocol has not been formally instituted, all PTEN mutation carriers should adopt the cancer surveillance strategies proposed for patients with Cowden syndrome. In addition, because gastrointestinal and vascular complications can be more severe in Bannayan–Riley–Ruvalcaba syndrome than in Cowden syndrome, patients with Bannayan–Riley–Ruvalcaba syndrome should be monitored from this point of view too. In this study, we report on two cases with Bannayan–Riley–Ruvalcaba phenotype that showed two different PTEN mutations. We also propose practice recommendations for management of PHTS patients. © 2013 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol

Piccione

Fragapane

Antona

et al. 2013

American J of Med Genetics Pt A

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“…A 21-amino acid polypeptide containing the PBM of PTEN physically binds to PtdIns(4,5)P 2 (43). K13E (9,14,27) and R15A (11,45) are reported as human cancer mutations. The K13E PTEN mutant does not bind to PtdIns(4,5)P 2 in vitro as examined by FRET between tryptophan fluorescence and a pyrene label on phosphatidylethanolamine (PE) (43).…”

Section: Phosphoinositides and Ptenmentioning

confidence: 99%

Voltage-Sensing Phosphatase: Its Molecular Relationship With PTEN

Okamura

Dixon

2011

Physiology

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Voltage-sensing phosphoinositide phosphatase (VSP) contains voltage sensor and cytoplasmic phosphatase domains. A unique feature of this protein is that depolarization-induced motions of the voltage sensor activate PtdIns(3,4,5)P 3 and PtdIns(4,5)P 2 phosphatase activities. VSP exhibits remarkable structural similarities with PTEN, the phosphatase and tensin homolog deleted on chromosome 10. These similarities include the cytoplasmic phosphatase region, the phosphoinositide binding region, and the putative membrane interacting C2 domain. Phosphoinositides and PTENPhosphoinositides constitute up to 4% of the total membrane phospholipids and are located at the inner leaflet of biological membranes. The headgroup of phosphoinositides is composed of an inositol ring with phosphate(s). Phosphoinositides are key second messengers for intracellular signaling, with distinct phosphoinositides having different signaling roles depending on the position and the number of phosphates on the inositol ring. PTEN (phosphatase, tensin homolog, deleted on chromosome TEN) was first identified as a tumor suppressor gene by mapping homozygous deletions on human chromosome 10q23. 3 (23, 24, 45). PTEN exhibits overall homology to protein tyrosine phosphatases and weak homology to tensin, a cell adhesion molecule, and auxilin, a protein involved in synaptic vesicle transport. Because the phosphatase domain of PTEN shows a signature Cysx5-Arg [CX(5)R] motif that is conserved in protein tyrosine phosphatases (PTPs), PTEN was first thought to be a protein phosphatase (24). However, PTEN exhibited only low catalytic activity toward phosphoproteins and peptides. It showed the highest activity toward negatively charged phosphorylated polymers such as Glu-Tyr n , but this activity was low relative to other protein phosphatases (23, 36). PTEN was shown by the Dixon laboratory to dephosphorylate PtdIns(3,4,5)P 3 , making it the first phosphatase identified to utilize a phosphoinositide as its substrate (29,30). A large number of studies with gene knockdown or conditional gene knockout mice have shown that PTEN plays a critical role in diverse biological events, including development, cell growth, cell size, and morphology, through negative regulation of Ptdlns(3,4,5)P 3 .PTEN consists of two major domains (the phosphatase domain and the C2 domain) and three short regulatory regions [the NH 2 -terminal phosphoinositide binding motif (PBM), the COOH-terminal tail region, and the COOH-terminal PDZ binding motif] (see FIGURE 1). The phosphatase domain of PTEN has a similar structure to that of non-metal-regulated phosphatases, including PTPs and dual-specificity phosphatases (22). A study of the crystal structure of PTEN (22) showed that the phosphatase domain has a deeper substrate binding pocket than PTPs and dual-specificity phosphatases, accounting for a much higher preference for phosphoiniositides than protein substrates.The structure of the C2 domain of PTEN is similar to the C2 domain in other proteins, including phospholipase C and phospho...

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“…PTEN mutations have been identified in 13-81% and 57-60% of cases of CS and BRR respectively (Lynch et al 1997, Nelen et al 1997, Longy et al 1998, Marsh et al 1998, Tsou et al 1998. PTEN mutations in CS tend to cluster at, but are not limited to, exon 5, which encodes the phosphatase signature motif (see Fig.…”

Section: Germline Pten Mutationsmentioning

confidence: 99%

PTEN, a unique tumor suppressor gene.

Dahia¹

2000

Endocrine-Related Cancer

248

218

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For many years, it has been thought that the chromosome region 10q22-24 includes one or more genes that appear to play a role in several human malignancies. PTEN is a new tumor suppressor gene encoding a dual-specificity phosphatase that was cloned simultaneously by three groups (Li & Sun 1997, Li et al. 1997, Steck et al. 1997), two of which used a positional cloning approach to identify genes in chromosome 10 (Li et al. 1997, Steck et al. 1997). While several protein kinases have been implicated as oncogenes, and phosphatases have long been known frequently to antagonize their function, there has been no direct demonstration of the role of phosphatases in tumor development (Myers & Tonks 1997). PTEN characterization as a bona fide tumor suppressor gene has confirmed that a deficient phosphatase activity can lead to cancer, as detailed by studies that are described below.

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Mutations of PTEN in patients with Bannayan-Riley-Ruvalcaba phenotype.

Abstract: We report three new mutations in PTEN,

Cited by 83 publications

References 11 publications

PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol

PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol

Voltage-Sensing Phosphatase: Its Molecular Relationship With PTEN

PTEN, a unique tumor suppressor gene.

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