scholarly journals A Pediatric Case of Cowden Syndrome with Graves’ Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Cláudia Patraquim ◽  
Vera Fernandes ◽  
Sofia Martins ◽  
Ana Antunes ◽  
Olinda Marques ◽  
...  
Keyword(s):  
Treatment Options ◽  
Antithyroid Drug ◽  
Human Tumor ◽  
Suppressor Gene ◽  
Cowden Syndrome ◽  
Graves Disease ◽  
Multisystem Disorder ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Coarse Facies

Cowden syndrome (CS) is a rare dominantly inherited multisystem disorder, characterized by an extraordinary malignant potential. In 80% of cases, the human tumor suppressor gene phosphatase and tensin homolog (PTEN) is mutated. We present a case of a 17-year-old boy with genetically confirmed CS and Graves’ disease (GD). At the age of 15, he presented with intention tremor, palpitations, and marked anxiety. On examination, he had macrocephaly, coarse facies, slight prognathism, facial trichilemmomas, abdominal keratoses, leg hemangioma, and a diffusely enlarged thyroid gland. He started antithyroid drug (ATD) therapy with methimazole and, after a 2-year treatment period without achieving a remission status, a total thyroidectomy was performed. Diagnosis and management of CS should be multidisciplinary. Thyroid disease is frequent, but its management has yet to be fully defined. The authors present a case report of a pediatric patient with CS and GD and discuss treatment options.

scholarly journals BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1α activation

2018 ◽  
Vol 115 (41) ◽  
pp. E9600-E9609 ◽  
Author(s):  
Andrew G. Li ◽  
Elizabeth C. Murphy ◽  
Aedin C. Culhane ◽  
Emily Powell ◽  
Hua Wang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Human Cancer ◽  
Human Tumor ◽  
Suppressor Gene ◽  
Phosphatase And Tensin Homolog ◽  
Human Cancer Cells ◽  
Tensin Homolog ◽  
Multiple Protein ◽  
Gsk 3Β ◽  
Cancer Suppression

BRCA1 is an established breast and ovarian tumor suppressor gene that encodes multiple protein products whose individual contributions to human cancer suppression are poorly understood. BRCA1-IRIS (also known as “IRIS”), an alternatively spliced BRCA1 product and a chromatin-bound replication and transcription regulator, is overexpressed in various primary human cancers, including breast cancer, lung cancer, acute myeloid leukemia, and certain other carcinomas. Its naturally occurring overexpression can promote the metastasis of patient-derived xenograft (PDX) cells and other human cancer cells in mouse models. The IRIS-driven metastatic mechanism results from IRIS-dependent suppression of phosphatase and tensin homolog (PTEN) transcription, which in turn perturbs the PI3K/AKT/GSK-3β pathway leading to prolyl hydroxylase-independent HIF-1α stabilization and activation in a normoxic environment. Thus, despite the tumor-suppressing genetic origin of IRIS, its properties more closely resemble those of an oncoprotein that, when spontaneously overexpressed, can, paradoxically, drive human tumor progression.

PTEN-Related Overgrowth Syndromes

2019 ◽  
pp. 163-186
Author(s):  
Lamis Yehia ◽  
Joanne Ngeow ◽  
Charis Eng
Keyword(s):  
Autosomal Dominant ◽  
Vascular Malformations ◽  
Treatment Strategies ◽  
Suppressor Gene ◽  
Cowden Syndrome ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Cell Growth And Proliferation

Individuals carrying germline mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN) may present with diverse clinical phenotypes, grouped under the term of PTEN hamartoma tumor syndrome (PHTS). This chapter will focus on two PHTS conditions: Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome. The first condition is an autosomal dominant disorder characterized by macrocephaly, intestinal hamartomatous polyposis, vascular malformations, lipomas, hemangiomas, and genital freckling. Other features include developmental delay, hypotonia, and scoliosis. Cowden syndrome is also an autosomal dominant disorder, mainly characterized by multiple hamartomas and high risk of breast, thyroid, and other cancers. PTEN encodes the main inhibitor of the PI3K-AKT pathway, regulating cell growth and proliferation, and protein synthesis. Therefore, germline loss-of-function mutations in this gene lead to excessive growth, particularly affecting connective tissues. Detection of PTEN mutations is critical for clinical management and treatment strategies.

scholarly journals Androgen actions via androgen receptor promote PTEN inactivation induced uterine cancer

2015 ◽  
Vol 22 (5) ◽  
pp. 687-701 ◽  
Author(s):  
Jaesung (Peter) Choi ◽  
Reena Desai ◽  
Yu Zheng ◽  
Mu Yao ◽  
Qihan Dong ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Uterine Cancer ◽  
Serum Testosterone ◽  
Cowden Syndrome ◽  
Corpora Lutea ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Uterine Growth ◽  
Uterine Cancers ◽  
Reproductive Cancers

Haploinsufficient inactivating phosphatase and tensin homolog (Pten) mutations cause Cowden syndrome, an autosomal dominant risk genotype for hormone dependent reproductive cancers. As androgen actions mediated via the androgen receptor (AR) supports uterine growth and may modify uterine cancer risk, we hypothesized that a functional AR may increase PTEN inactivation induced uterine cancer. To test the hypothesis, we compared the PTEN knockout (PTENKO) induced uterine pathology in heterozygous PTENKO and combined heterozygous PTEN and complete AR knockout (PTENARKO) female mice. PTENKO induced uterine pathology was significantly reduced by AR inactivation with severe macroscopic uterine pathology present in 21% of PTENARKO vs 46% of PTENKO at a median age of 45 weeks. This could be due to reduced stroma ERα expression in PTENARKO compared to PTENKO uterus, while AR inactivation did not modify PTEN or P-AKT levels. Unexpectedly, while progesterone (P4) is assumed protective in uterine cancers, serum P4was significantly higher in PTENKO females compared to WT, ARKO, and PTENARKO females consistent with more corpora lutea in PTENKO ovaries. Serum testosterone and ovarian estradiol were similar between all females. Hence, our results demonstrated AR inactivation mediated protection against PTENKO induced uterine pathology and suggests a potential role for antiandrogens in uterine cancer prevention and treatment.

scholarly journals Cowden Syndrome: report of a case and brief review of literature

2013 ◽  
Vol 88 (6 suppl 1) ◽  
pp. 52-52 ◽  
Author(s):  
Ana Carolina Souza Porto ◽  
Elisabeth Roider ◽  
Thomas Ruzicka
Keyword(s):  
Cell Cycle Progression ◽  
Cowden Syndrome ◽  
Pten Gene ◽  
Benign Tumors ◽  
Cutaneous Lesions ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Increased Risk ◽  
History Of ◽  
Risk Of Cancer

We present the case of a female patient with facial cutaneous lesions, a cobblestone-like pattern of the oral mucosa, and verruciform lesions on the hand since her youth. She reported a history of breast cancer, endometrial cancer, melanoma and multiple benign tumors and cysts. PTEN gene analysis was performed and confirmed Cowden Syndrome, a rare genodermatosis with an autosomal dominant pattern of inheritance, characterized by multiple hamartomas. The phosphatase and tensin homolog (PTEN) gene negatively regulates cell proliferation and cell cycle progression. Loss of PTEN function contributes to an increased risk of cancer. We emphasize the importance of early detection and accurate management of Cowden Syndrome.

scholarly journals PTENSequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
H. Gbelcová ◽  
P. Bakeš ◽  
P. Priščáková ◽  
V. Šišovský ◽  
I. Hojsíková ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Endometrial Carcinoma ◽  
Endometrial Hyperplasia ◽  
Female Genital Tract ◽  
Suppressor Gene ◽  
Serous Carcinoma ◽  
Tissue Samples ◽  
Phosphatase And Tensin Homolog ◽  
Coding Regions ◽  
Tensin Homolog

Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree ofPTENalterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions ofPTENgene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

scholarly journals The Skin in Cowden Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Agnes Lim ◽  
Joanne Ngeow
Keyword(s):  
Targeted Therapies ◽  
Autosomal Dominant ◽  
Malignant Tumors ◽  
Skin Lesions ◽  
Cowden Syndrome ◽  
Differential Diagnoses ◽  
Phosphatase And Tensin Homolog ◽  
Autosomal Dominant Condition ◽  
Tensin Homolog ◽  
Dominant Condition

Cowden syndrome (CS) is an autosomal dominant condition caused by mutations in the phosphatase and tensin homolog (PTEN) gene, and is characterized by multiple hamartomas and a predisposition to malignant tumors. Characteristic skin lesions include trichilemmomas, acral keratosis, mucocutaneous neuromas, oral papillomas, and penile macules, and are often the first clues to the underlying diagnosis. Here, we discuss the mucocutaneous manifestations of CS, differential diagnoses of genetic causes of each cutaneous finding, genetic analyses for patients with skin manifestations, management of patients with CS, and potential new targeted therapies for CS.

scholarly journals Testicular pain as a presentation of Cowden syndrome

2011 ◽  
Vol 93 (5) ◽  
pp. e51-e52 ◽  
Author(s):  
Hussain M Alnajjar ◽  
Arun Sahai ◽  
Andrew Keane ◽  
Stephen Gordon
Keyword(s):  
Cowden Syndrome ◽  
Limited Information ◽  
Nodular Goitre ◽  
Phosphatase And Tensin Homolog ◽  
Testicular Pain ◽  
Left Testicle ◽  
Tensin Homolog ◽  
History Of ◽  
Multiple Hamartoma Syndrome

This case report outlines a rare case in Cowden syndrome and PTEN (phosphatase and tensin homolog) gene mutation and how it may initially present to the urologist. Also known as multiple hamartoma syndrome, Cowden syndrome is a rare disorder associated with the development of several types of malignancy. A thorough search of the literature reveals limited information regarding its presentation to the urologist. We report the case of a 47-year-old gentleman with a two-week history of worsening pain and swelling in his left testicle. Testicular ultrasound revealed multiple hyperechoic areas bilaterally suggestive of multiple lipomas. He was also found to have macrocephaly, freckling of his glans and foreskin and an enlarged nodular goitre and the geneticist diagnosed Cowden syndrome. The disease is discussed and guidance is given on its management and follow up.

scholarly journals PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jorge A. Benitez ◽  
Jianhui Ma ◽  
Matteo D’Antonio ◽  
Antonia Boyer ◽  
Maria Fernanda Camargo ◽  
...  
Keyword(s):  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Growth Defect ◽  
Tumour Suppressor Genes ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Pten Deletion ◽  
Therapeutic Opportunity ◽  
Associated Function

Abstract Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog) are frequent events and are associated with therapeutic resistance. Herein, we report a novel chromatin-associated function of PTEN in complex with the histone chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX-H3.3 association on the chromatin, independently of PTEN enzymatic activity. Furthermore, DAXX inhibition specifically suppresses tumour growth and improves the survival of orthotopically engrafted mice implanted with human PTEN-deficient glioma samples, associated with global H3.3 genomic distribution changes leading to upregulation of tumour suppressor genes and downregulation of oncogenes. Moreover, DAXX expression anti-correlates with PTEN expression in GBM patient samples. Since loss of chromosome 10 and PTEN are common events in cancer, this synthetic growth defect mediated by DAXX suppression represents a therapeutic opportunity to inhibit tumorigenesis specifically in the context of PTEN deletion.

scholarly journals Independent Pretreatment Predictors of Graves’ Disease Outcome

Medicina ◽  
2013 ◽  
Vol 49 (10) ◽  
pp. 67 ◽  
Author(s):  
Dalia Daukšienė ◽  
Albertas Daukša ◽  
Narseta Mickuvienė
Keyword(s):  
Treatment Failure ◽  
Medical Treatment ◽  
Therapy Group ◽  
Treatment Options ◽  
Antithyroid Drug ◽  
Current Treatment ◽  
Disease Outcome ◽  
Graves Disease ◽  
Failure Group ◽  
Relapse Group

Background and Objective. Current treatment options of Graves’ disease (GD) are often unsatisfactory. This study aimed at determining the independent baseline predictors of medical treatment failure in GD. Material and Methods. A retrospective study of 194 patients with GD was carried out. According to the disease outcome, patients were divided into groups. The remission group included the patients who achieved long-term remission after initial antithyroid drug (ATD) treatment with no relapse (group 1) or after 2 or 3 courses of ATD therapy (group 2). The treatment failure group included the patients who underwent thyroid ablation due to relapse (group 3) or without ATD withdrawal (group 4). Results. A family history of thyroid disorders was associated with greater odds of failure (P=0.046). Higher thyrotropin receptor antibodies (TRAb) levels and a larger goiter size (grade 2/ grade 3) at the onset of the disease were both independently associated with a greater likelihood of failure. The initial TRAb concentration of 30.2 U/L and the TRAb concentration of 12.97 U/L at the end of ATD therapy were found to be the best cutoff values predicting the treatment failure. A hypoechogenic thyroid after ATD therapy, but not before therapy, increased the likelihood of failure by nearly 7.5 times (P<0.001). Conclusions. Higher TRAb levels and a larger goiter size at the onset of the disease were found to be the independent predictors of medical treatment failure in GD.

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