Novel Germline PTEN Mutation Associated with Cowden Syndrome and Osteosarcoma

Lopez, Christian; Abuel-Haija, Mohammad; Peña, Luis; Coppola, Domenico

doi:10.21873/cgp.20069

Cited by 6 publications

(3 citation statements)

References 14 publications

(12 reference statements)

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“…PTEN is a tumor suppressor with phosphatase activity and decrease or loss of PTEN expression, due to the methylation, mutation or deletion, may closely relate to the occurrence and development of multiple cancers [17,18]. The clinical study found that the expression of PTEN protein in prostate cancer tissues was significantly lower than that in benign prostatic hyperplasia and negatively correlated to clinical Gleason score, pathological grade, and stage of prostate cancer [19,20], suggesting that PTEN protein decreases with the increase of the malignancy of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Kang

et al. 2020

Aging

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Family with sequence similarity 46 member C (FAM46C) is a non-canonical poly(A) polymerase that is associated with tumorigenesis. However, its role in prostate cancer development is not fully understood. Herein, we determined expression pattern of FAM46C in prostate cancer and further identified its effect on the tumorigenesis and chemosensitivity. FAM46C expression was decreased in prostate cancer tissues and cell lines compared with corresponding controls. FAM46C expression was significantly associated with the Gleason score, tumor size and overall survival. FAM46C knockdown in 22RV1 and DU145 cells significantly inhibited apoptosis and promoted cell proliferation and cell cycle progression as well as activation of AKT. FAM46C overexpression had an inverse effect in DU145 cells and inhibited tumor growth in vivo. FAM46C inhibited cell proliferation and cell cycle progression and induced apoptosis via the PTEN/AKT signaling pathway. FAM46C promoted PTEN expression through inhibiting PTEN ubiquitination. The prostate cancer cells and patient-derived xenograft (PDX) mice with high-FAM46C-expressing demonstrated an enhanced chemosensitivity to docetaxel. These findings suggest that FAM46C control cell proliferation, cell cycle and apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity of prostate cancer. Modulation of their levels may offer a new approach for improving anti-tumor efficacy for chemotherapeutic agents in prostate cancer.

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Section: Introductionmentioning

confidence: 99%

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Kang

et al. 2020

Aging

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“…Other malignant tumors include malignant melanoma [25], pituitary tumor [26], osteosarcoma [27], gastrointestinal stromal tumor [28], and dermatofibrosarcoma protuberans [29].…”

Section: N) Other Malignant Tumors and Tumorsmentioning

confidence: 99%

Clinical Guidelines for Diagnosis and Management of Cowden Syndrome/PTEN Hamartoma Tumor Syndrome in Children and Adults-Secondary Publication

Takayama,

Muguruma,

Igarashi

et al. 2023

J Anus Rectum Colon

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Cowden syndrome (CS)/ PTEN hamartoma tumor syndrome (PHTS) is a rare autosomal dominantly inherited condition caused by germline pathogenesis. It is associated with multiple hamartomatous lesions occurring in various organs and tissues, including the gastrointestinal tract, skin, mucous membranes, breast, thyroid, endometrium, and brain. Macrocephaly or multiple characteristic mucocutaneous lesions commonly develop in individuals in their 20s. This syndrome is occasionally diagnosed in childhood due to the occurrence of multiple gastrointestinal polyps, autism spectrum disorders, and intellectual disability. CS/PHTS can be diagnosed taking the opportunity of multigene panel testing in patients with cancer. Appropriate surveillance for early diagnosis of associated cancers is required because patients have a high risk of cancers including breast, thyroid, colorectal, endometrial, and renal cancers. Under these circumstances, there is growing concern regarding the management of CS/PHTS in Japan, but there are no available practice guidelines. To address this situation, the guideline committee, which included specialists from multiple academic societies, was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour, and Welfare, Japan. The present clinical guidelines explain the principles in the diagnosis and management of CS/PHTS, together with four clinical questions and the corresponding recommendations, incorporating the concept of the Grading of Recommendations Assessment, Development, and Evaluation system. Herein, we present an English version of the guideline, some of which have been updated, to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with CS/PHTS.

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“…Osteosarcoma is an extremely rare presentation of PHTS (only one case has been reported in the English-written literature) [8].…”

Section: Not Reportedmentioning

confidence: 99%

Genetic Determinants of Inherited Endocrine Tumors: Do They Have a Direct Role in Bone Metabolism Regulation and Osteoporosis?

Marini

Giusti

Iantomasi

et al. 2021

Genes

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Endocrine tumors are neoplasms originating from specialized hormone-secreting cells. They can develop as sporadic tumors, caused by somatic mutations, or in the context of familial Mendelian inherited diseases. Congenital forms, manifesting as syndromic or non-syndromic diseases, are caused by germinal heterozygote autosomal dominant mutations in oncogenes or tumor suppressor genes. The genetic defect leads to a loss of cell growth control in target endocrine tissues and to tumor development. In addition to the classical cancer manifestations, some affected patients can manifest alterations of bone and mineral metabolism, presenting both as pathognomonic and/or non-specific skeletal clinical features, which can be either secondary complications of endocrine functioning primary tumors and/or a direct consequence of the gene mutation. Here, we specifically review the current knowledge on possible direct roles of the genes that cause inherited endocrine tumors in the regulation of bone modeling and remodeling by exploring functional in vitro and in vivo studies highlighting how some of these genes participate in the regulation of molecular pathways involved in bone and mineral metabolism homeostasis, and by describing the potential direct effects of gene mutations on the development of skeletal and mineral metabolism clinical features in patients.

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Novel Germline PTEN Mutation Associated with Cowden Syndrome and Osteosarcoma

Abstract: We report a patient with CS presenting with ganglioneuromatosis, benign breast mass and osteosarcoma, harboring a novel molecular alteration in PTEN which to our knowledge has not been previously reported.

Cited by 6 publications

References 14 publications

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Clinical Guidelines for Diagnosis and Management of Cowden Syndrome/PTEN Hamartoma Tumor Syndrome in Children and Adults-Secondary Publication

Genetic Determinants of Inherited Endocrine Tumors: Do They Have a Direct Role in Bone Metabolism Regulation and Osteoporosis?

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