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Charis Eng - One of the best experts on this subject based on the ideXlab platform.
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PTEN Hamartoma Tumor Syndrome: A Case of Renal Cell Carcinoma in a Young Female.
Urology, 2020Co-Authors: Rathika R Ramkumar, Charis Eng, Prithvi B. Murthy, Jane K. Nguyen, Jesse K. Mckenney, Steven C. CampbellAbstract:Abstract PTEN Hamartoma-Tumor-Syndrome (PHTS) describes a series of conditions characterized by germline-mutation of the PTEN Tumor-suppressor gene. PHTS patients have an increased lifetime risk of multiple malignancies, including thyroid, breast, and endometrial cancers. PHTS patients also have 20-30 fold increased risk of renal cell carcinoma (RCC) compared to age-matched controls. As with many hereditary RCC Syndromes, Tumors present early and multifocally. We present a case of one of the youngest patients diagnosed with RCC in PHTS and review the urologic implications of this Syndrome.
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WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition
The New England journal of medicine, 2020Co-Authors: Yu-ru Lee, Lamis Yehia, Takahiro Kishikawa, Brandie Leach, Jinfang Zhang, Nivedita Panch, Jing Liu, Wenyi Wei, Charis EngAbstract:Abstract Background Patients with PTEN hamartoma Tumor Syndrome (PHTS) have germline mutations in the Tumor-suppressor gene encoding phosphatase and tensin homologue (PTEN). Such mutations have bee...
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The microbiome in PTEN hamartoma Tumor Syndrome.
Endocrine-related cancer, 2017Co-Authors: Victoria Byrd, Ted M Getz, Roshan Padmanabhan, Hans Arora, Charis EngAbstract:Germline PTEN mutations defining PTEN hamartoma Tumor Syndrome (PHTS) confer heritable predisposition to breast, endometrial, thyroid and other cancers with known age-related risks, but it remains impossible to predict if any individual will develop cancer. In the general population, gut microbial dysbiosis has been linked to cancer, yet is unclear whether these are associated in PHTS patients. In this pilot study, we aimed to characterize microbial composition of stool, urine, and oral wash from 32 PTEN mutation-positive individuals using 16S rRNA gene sequencing. PCoA revealed clustering of the fecal microbiome by cancer history (P = 0.03, R2 = 0.04). Fecal samples from PHTS cancer patients had relatively more abundant operational taxonomic units (OTUs) from family Rikenellaceae and unclassified members of Clostridia compared to those from non-cancer patients, whereas families Peptostreptococcaceae, Enterobacteriaceae, and Bifidobacteriaceae represented relatively more abundant OTUs among fecal samples from PHTS non-cancer patients. Functional metagenomic prediction revealed enrichment of the folate biosynthesis, genetic information processing and cell growth and death pathways among fecal samples from PHTS cancer patients compared to non-cancer patients. We found no major shifts in overall diversity and no clustering by cancer history among oral wash or urine samples. Our observations suggest the utility of an expanded study to interrogate gut dysbiosis as a potential cancer risk modifier in PHTS patients.
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pten hamartoma Tumor Syndrome clinical risk assessment and management protocol
Methods, 2015Co-Authors: Joanne Ngeow, Charis EngAbstract:The Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important phosphatase that counteracts one of the most critical cancer pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathways. Clinically, deregulation of PTEN function resulting in reduced PTEN expression and activity is implicated in human diseases. Cowden Syndrome (CS) is an autosomal dominant disorder characterized by benign and malignant Tumors. CS-related individual features occur commonly in the general population. Approximately 25% of patients diagnosed with CS have pathogenic germline PTEN mutations, which increase lifetime risks of breast, thyroid, uterine, renal and other cancers. PTEN testing and intensive cancer surveillance allow for early detection and treatment of these cancers for mutation positive patients and their relatives. In this review, we highlight our current knowledge of germline PTEN mutations in relation to human disease. We review current clinical diagnosis and management recommendations for PHTS including recent discoveries in understanding PTEN function regulation and how this can be exploited therapeutically.
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ACG Guidelines on Management of PTEN-Hamartoma Tumor Syndrome: Does the Evidence Support so Much so Young?
The American journal of gastroenterology, 2015Co-Authors: Brandie Heald, Carol A. Burke, Matthew F. Kalady, Charis EngAbstract:ACG Guidelines on Management of PTEN -Hamartoma Tumor Syndrome: Does the Evidence Support so Much so Young?
Joachim Woelfle - One of the best experts on this subject based on the ideXlab platform.
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phenotype driven diagnostic of pten hamartoma Tumor Syndrome macrocephaly but neither height nor weight development is the important trait in children
Cancers, 2019Co-Authors: Michaela Plamper, Felix Schreiner, Bettina Gohlke, Joachim WoelfleAbstract:PTEN hamartoma Tumor Syndrome (PHTS) encompasses different syndromic disorders which are associated with autosomal-dominant mutations of the Tumor suppressor gene PTEN. Patients are at high risk to develop benign and malignant Tumors. Macrocephaly is a diagnostic feature, but there is a paucity of data on auxological development during childhood. Growth charts for height, weight and head circumference for PHTS do not exist yet. In this study, patient data for height, weight and head circumferences (HC) were collected from repeated medical exams or prevention check-up visits starting at birth. Growth charts were generated and compared to German reference data. Standard deviation scores (SDS) of HC, height and body mass index (BMI) were calculated. We included 23 pediatric patients (8 female, 15 male) with molecular proven PTEN gene mutation. Most male patients already demonstrated macrocephaly at birth (73%), whereas only one female patient had documented congenital macrocephaly. By the age of two years all patients exhibited a head circumference above the 97th percentile. Stratified for different age groups the median HC-SDSs were between +3.3 and +5.5 in male patients and between +2.9 and +4.1 in female patients. Height, weight and BMI measurements for both sexes were mostly within the normal range. We conclude that macrocephaly, but not height, weight or BMI, is useful in the identification of PHTS patients. The increased HC in PHTS patients develops early in life and is more pronounced in males than in females, which might explain the finding of a higher percentage of male PHTS patients diagnosed during childhood.
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Thyroid disease in children and adolescents with PTEN hamartoma Tumor Syndrome (PHTS)
European Journal of Pediatrics, 2018Co-Authors: Michaela Plamper, Felix Schreiner, Bettina Gohlke, Janina Kionke, Eckard Korsch, James Kirkpatrick, Mark Born, Stefan Aretz, Joachim WoelfleAbstract:Patients with PTEN hamartoma Tumor Syndrome (PHTS) are at increased risk of developing benign and malignant Tumors, including thyroid carcinoma. Benign thyroid lesions and single cases of thyroid carcinoma have been reported in children with PHTS. We conducted a retrospective, single-centered study including children and adolescents with a molecularly proven diagnosis of PTEN. Our cohort consists of 16 patients, with a mean age at diagnosis PHTS of 5.7 years. Twelve of 16 cases exhibited thyroid abnormalities (75%). In seven patients, thyroid abnormalities were already present at first ultrasound screening, in five cases they occurred during follow-up. Eight patients underwent thyroidectomy. Histopathology included nodular goiter, follicular adenoma, papillary microcarcinoma in a boy of six and follicular carcinoma in a girl of 13 years. Two patients had autoimmune thyroid disease. Conclusion : Thyroid disease is common in children with PHTS. Physicians caring for patients with early thyroid abnormalities and additional syndromal features should be aware of PHTS as a potentially underlying disorder. Ultrasound screening should be performed immediately after diagnosis of PHTS and repeated yearly or more frequently. Because of possible early cancer development, we recommend early surgical intervention in the form of total thyroidectomy in cases of suspicious ultrasound findings. What is Known: • PHTS patients are at high risk of developing benign and malignant Tumors. • Individual cases of thyroid carcinoma in children have been reported. What is New: • Thyroid disease is even more common in children with PHTS (75%) than previously expected. • Frequently thyroid disease is the first organ pathology requiring diagnostic workup and therefore children with PHTS should be examined for thyroid disease right after diagnosis and receive follow-up on a regular basis throughout life.
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Thyroid disease in children and adolescents with PTEN hamartoma Tumor Syndrome (PHTS).
European journal of pediatrics, 2017Co-Authors: Michaela Plamper, Felix Schreiner, Bettina Gohlke, Janina Kionke, Eckard Korsch, James Kirkpatrick, Mark Born, Stefan Aretz, Joachim WoelfleAbstract:Patients with PTEN hamartoma Tumor Syndrome (PHTS) are at increased risk of developing benign and malignant Tumors, including thyroid carcinoma. Benign thyroid lesions and single cases of thyroid carcinoma have been reported in children with PHTS. We conducted a retrospective, single-centered study including children and adolescents with a molecularly proven diagnosis of PTEN. Our cohort consists of 16 patients, with a mean age at diagnosis PHTS of 5.7 years. Twelve of 16 cases exhibited thyroid abnormalities (75%). In seven patients, thyroid abnormalities were already present at first ultrasound screening, in five cases they occurred during follow-up. Eight patients underwent thyroidectomy. Histopathology included nodular goiter, follicular adenoma, papillary microcarcinoma in a boy of six and follicular carcinoma in a girl of 13 years. Two patients had autoimmune thyroid disease.
Vânia Nose - One of the best experts on this subject based on the ideXlab platform.
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Genodermatosis Affecting the Skin and Mucosa of the Head and Neck: Clinicopathologic, Genetic, and Molecular Aspect—PTEN-Hamartoma Tumor Syndrome/Cowden Syndrome
Head and Neck Pathology, 2016Co-Authors: Vânia NoseAbstract:PTEN hamartoma Tumor Syndrome refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog ( PTEN ) gene. Cowden Syndrome, the principal PTEN-related disorder is characterized by multiple neoplasms and hamartomas, mucosal papillomatosis, and skin lesions, trichilemmomas. Trichilemmomas and mucocutaneous papillomatous papules are one of the first signs of the disease. Early recognition of these skin lesions may help on diagnosing an underlying malignancy and early cancer screening.
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Endocrine Tumors as part of inherited Tumor Syndromes.
Advances in Anatomic Pathology, 2011Co-Authors: Yaxia Zhang, Vânia NoseAbstract:: The endocrine system is an embryological diverse system consisted of a variety of glands, such as pituitary, parathyroid, thyroid, adrenal, endocrine pancreas, and the diffuse neuroendocrine system. Endocrine Tumor can be presented as a sporadic event, or as part of an inherited Tumor Syndrome. During the past century, inherited Tumor Syndromes have emerged as an important group of diseases. With the growing knowledge of each inherited Tumor Syndrome in the molecular genetic level, many changes in clinical management have occurred. This review focuses on the endocrine Tumors involving the pituitary, parathyroid, thyroid, adrenal, and endocrine pancreas, in the setting of inherited Tumor Syndromes. We discuss the specific clinical, molecular genetic, and pathologic features of endocrine Tumor in each gland and their associated inherited Tumor Syndromes. By understanding the pathogenesis of inherited endocrine Tumor Syndromes and recognizing the unique features of pathologic findings, pathologists bear the responsibility to provide the clinicians the guidelines in terms of screening and treatment of inherited Tumor Syndromes.
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thyroid nodules and cancer in children with pten hamartoma Tumor Syndrome
The Journal of Clinical Endocrinology and Metabolism, 2011Co-Authors: Jessica R Smith, Vânia Nose, Ellen Marqusee, Susan Webb, Steven J Fishman, Robert C Shamberger, Mary C Frates, Stephen A HuangAbstract:Context: Phosphatase and tensin homolog (PTEN) hamartoma Tumor Syndrome (PHTS) is a complex disorder caused by germline-inactivating mutations of the PTEN Tumor suppressor gene. Carriers develop benign and malignant Tumors of multiple tissues, including the breast, thyroid, intestine, and skin. Surveillance to facilitate the early detection and treatment of malignancies is recommended but, because thyroid cancers have been reported almost exclusively in adults, childhood risk is considered to be low, and consensus guidelines recommend that surveillance imaging begin at 18 yr of age. Objective/Patients: Seven children with PHTS referred to two thyroidologists form the basis of this report. Medical records, operative histology, and PTEN mutational analysis were reviewed to evaluate the pediatric presentation of PHTS-associated thyroid neoplasia. Results: Five of the seven children presented with thyroid nodules or thyroid cancer between the ages of 6 and 12 yr, often as the initially identified component of...
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thyroid pathology in pten hamartoma Tumor Syndrome characteristic findings of a distinct entity
Thyroid, 2011Co-Authors: Anna R Laury, Massimo Bongiovanni, Jeanchristophe Tille, Harry P W Kozakewich, Vânia NoseAbstract:Background: Phosphatase and tensin homolog deleted on chromosome ten (PTEN)-hamartoma Tumor Syndrome (PHTS) is a complex disorder caused by germline inactivating mutations of the PTEN Tumor suppressor gene. PHTS includes Cowden Syndrome (CS), Bannayan-Riley-Ruvalcaba Syndrome (BRRS), and Proteus-like Syndromes. Affected individuals develop both benign and malignant Tumors in a variety of tissues, including the thyroid. This study is to better characterize and describe the thyroid pathology within the different entities of this Syndrome, and examine whether there is an association between specific thyroid findings and different PTEN mutations. Methods: Twenty patients with known PTEN mutations, and/or clinical diagnosis of PHTS, and thyroid pathology were identified: 14 with CS and 6 with BRRS. Results: Thyroid pathology findings were as follows: multiple adenomatous nodules in a background of lymphocytic thyroiditis (LT) in 75%, papillary carcinoma in 60%, LT alone in 55%, follicular carcinoma in 45%, C-c...
Janina Kionke - One of the best experts on this subject based on the ideXlab platform.
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Thyroid disease in children and adolescents with PTEN hamartoma Tumor Syndrome (PHTS)
European Journal of Pediatrics, 2018Co-Authors: Michaela Plamper, Felix Schreiner, Bettina Gohlke, Janina Kionke, Eckard Korsch, James Kirkpatrick, Mark Born, Stefan Aretz, Joachim WoelfleAbstract:Patients with PTEN hamartoma Tumor Syndrome (PHTS) are at increased risk of developing benign and malignant Tumors, including thyroid carcinoma. Benign thyroid lesions and single cases of thyroid carcinoma have been reported in children with PHTS. We conducted a retrospective, single-centered study including children and adolescents with a molecularly proven diagnosis of PTEN. Our cohort consists of 16 patients, with a mean age at diagnosis PHTS of 5.7 years. Twelve of 16 cases exhibited thyroid abnormalities (75%). In seven patients, thyroid abnormalities were already present at first ultrasound screening, in five cases they occurred during follow-up. Eight patients underwent thyroidectomy. Histopathology included nodular goiter, follicular adenoma, papillary microcarcinoma in a boy of six and follicular carcinoma in a girl of 13 years. Two patients had autoimmune thyroid disease. Conclusion : Thyroid disease is common in children with PHTS. Physicians caring for patients with early thyroid abnormalities and additional syndromal features should be aware of PHTS as a potentially underlying disorder. Ultrasound screening should be performed immediately after diagnosis of PHTS and repeated yearly or more frequently. Because of possible early cancer development, we recommend early surgical intervention in the form of total thyroidectomy in cases of suspicious ultrasound findings. What is Known: • PHTS patients are at high risk of developing benign and malignant Tumors. • Individual cases of thyroid carcinoma in children have been reported. What is New: • Thyroid disease is even more common in children with PHTS (75%) than previously expected. • Frequently thyroid disease is the first organ pathology requiring diagnostic workup and therefore children with PHTS should be examined for thyroid disease right after diagnosis and receive follow-up on a regular basis throughout life.
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Thyroid disease in children and adolescents with PTEN hamartoma Tumor Syndrome (PHTS).
European journal of pediatrics, 2017Co-Authors: Michaela Plamper, Felix Schreiner, Bettina Gohlke, Janina Kionke, Eckard Korsch, James Kirkpatrick, Mark Born, Stefan Aretz, Joachim WoelfleAbstract:Patients with PTEN hamartoma Tumor Syndrome (PHTS) are at increased risk of developing benign and malignant Tumors, including thyroid carcinoma. Benign thyroid lesions and single cases of thyroid carcinoma have been reported in children with PHTS. We conducted a retrospective, single-centered study including children and adolescents with a molecularly proven diagnosis of PTEN. Our cohort consists of 16 patients, with a mean age at diagnosis PHTS of 5.7 years. Twelve of 16 cases exhibited thyroid abnormalities (75%). In seven patients, thyroid abnormalities were already present at first ultrasound screening, in five cases they occurred during follow-up. Eight patients underwent thyroidectomy. Histopathology included nodular goiter, follicular adenoma, papillary microcarcinoma in a boy of six and follicular carcinoma in a girl of 13 years. Two patients had autoimmune thyroid disease.
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immune dysregulation in patients with pten hamartoma Tumor Syndrome analysis of foxp3 regulatory t cells
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Hannah Chen, Norman Händel, Joanne Ngeow, James E Muller, Michael Huhn, Huei Ting Yang, Mario Heindl, Roos Marijn Berbers, Ahmed N Hegazy, Janina KionkeAbstract:Background Patients with heterozygous germline mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) experience autoimmunity and lymphoid hyperplasia. Objectives Because regulation of the phosphoinositide 3-kinase (PI3K) pathway is critical for maintaining regulatory T (Treg) cell functions, we investigate Treg cells in patients with heterozygous germline PTEN mutations (PTEN hamartoma Tumor Syndrome [PHTS]). Methods Patients with PHTS were assessed for immunologic conditions, lymphocyte subsets, forkhead box P3 (FOXP3) + Treg cell levels, and phenotype. To determine the functional importance of phosphatases that control the PI3K pathway, we assessed Treg cell induction in vitro , mitochondrial depolarization, and recruitment of PTEN to the immunologic synapse. Results Autoimmunity and peripheral lymphoid hyperplasia were found in 43% of 79 patients with PHTS. Immune dysregulation in patients with PHTS included lymphopenia, CD4 + T-cell reduction, and changes in T- and B-cell subsets. Although total CD4 + FOXP3 + Treg cell numbers are reduced, frequencies are maintained in the blood and intestine. Despite pathogenic PTEN mutations, the FOXP3 + T cells are phenotypically normal. We show that the phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP) downstream of PTEN is highly expressed in normal human Treg cells and provides complementary phosphatase activity. PHLPP is indispensable for the differentiation of induced Treg cells in vitro and Treg cell mitochondrial fitness. PTEN and PHLPP form a phosphatase network that is polarized at the immunologic synapse. Conclusion Heterozygous loss of function of PTEN in human subjects has a significant effect on T- and B-cell immunity. Assembly of the PTEN-PHLPP phosphatase network allows coordinated phosphatase activities at the site of T-cell receptor activation, which is important for limiting PI3K hyperactivation in Treg cells despite PTEN haploinsufficiency.
Andras Berta - One of the best experts on this subject based on the ideXlab platform.
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three novel germ line vhl mutations in hungarian von hippel lindau patients including a nonsense mutation in a fifteen year old boy with renal cell carcinoma
BMC Medical Genetics, 2013Co-Authors: Gergely Losonczy, Ferenc Fazakas, G Pfliegler, Istvan Komaromi, Erzsebet Balazs, Krisztina Penzes, Andras BertaAbstract:Background Von Hippel-Lindau disease is an autosomal dominantly inherited highly penetrant Tumor Syndrome predisposing to retinal and central nervous system hemangioblastomas, renal cell carcinoma and phaeochromocytoma among other less frequent complications.
