Prkar1a

'Pituitary tumours' is an umbrella term for various tumours originating from different regions of the hypothalamic-pituitary system. The vast majority of pituitary tumours are pituitary adenomas, also recently referred to as pituitary neuroendocrine tumours. The prevalence of clinically relevant pituitary adenomas is approximately 1 in 1000; other pituitary tumours such as craniopharyngioma and pituicytoma are comparatively very rare. This review addresses the molecular and genetic aspects of pituitary adenomas...

Immunotherapeutic strategies aimed at enhancing tumor cell killing by tumor-specific T cells hold great potential for reducing tumor burden and prolonging survival of cancer patients. Although many potential tumor antigens have been described, identifying relevant targets when designing anti-cancer vaccines or targeted cell therapies remains a challenge. To identify novel, potentially immunogenic candidate tumor antigens, we performed integrated tumor transcriptomic, seromic, and proteomic analyses of high grade serous ovarian cancer (HGSC) patient tumor samples...

Despite all epidemiological, clinical, and experimental research efforts, therapeutic concepts in sepsis and sepsis-induced multi-organ dysfunction syndrome (MODS) remain limited and unsatisfactory. Currently, gene expression data sets are widely utilized to discover new biomarkers and therapeutic targets in diseases. In the present study, we analyzed MODS expression profiles (comprising 13 sepsis and 8 control samples) retrieved from NCBI-GEO and found 359 differentially expressed genes (DEGs), among which 170 were downregulated and 189 were upregulated...

Large cell calcifying Sertoli cell tumour (LCCSCT) is a type of testicular sex cord-stromal tumour that may occur sporadically or in the context of Carney complex and other genetic syndromes. A subset is clinically malignant, and the molecular mechanisms that drive such aggressive behaviour remain unknown. METHODS AND RESULTS: We analysed 21 samples from 20 patients with LCCSCT (12 non-metastasising and eight metastasising) using PRKAR1A immunohistochemistry (IHC) and next-generation sequencing. All tumours except two (cases 17 and 20, both metastasising) demonstrated loss of PRKAR1A expression...

INTRODUCTION: Herein we describe a series of rare peripheral pulmonary neoplasms temporarily termed "peripheral type squamous cell neoplasm of uncertain malignant potential (PSCN-UMP)" and investigate their relationship to bronchiolar adenoma (BA) and squamous cell carcinoma (SCC). MATERIALS AND METHODS: The histologic and immunohistochemical features of 10 PSCN-UMPs and six BAs were compared. Whole exome sequencing (WES) and bioinformatics analysis were performed to further compare the genetic features of PSCN-UMPs, BAs, and NSCLCs...

INTRODUCTION: Severe short stature is a feature of acrodysostosis, but data on growth are sparse. Treatment with recombinant human growth hormone (rhGH) is used in some centers to increase final height, but no studies have been published so far. Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD); acrodysostosis refers to iPPSD4 (acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (acrodysostosis type 2, due to PDE4D mutations)...

BACKGROUND: Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome characterized by mucocutaneous lentigines/ blue nevi, cardiac myxoma and endocrine overactivity. Here, we report a CNC case with PRKAR1A gene mutation characterized by left atrial adenomyxoma to explore the diagnosis and treatment of CNC. CASE PRESENTATION: A 42-year-old woman with a history of cardiac tumour surgery presented with typical features of Cushing syndrome, including central obesity, buffalo hump, mild facial plethora, purple striae on the lower abdomen, and spotty skin pigmentation...

Superficial angiomyxoma is an uncommon benign mesenchymal neoplasm that usually arises in dermis/subcutis of the extremities or trunk. Some tumors are associated with Carney complex. When arising in breast, these tumors are not well-recognized, mainly due to a lack of uniform nomenclature in the literature. This study therefore aims to improve recognition of angiomyxomas of the breast region. Forty cases were identified: demographics, presence of Carney complex, imaging and histologic features, PRKAR1A expression, and outcomes were evaluated...

BACKGROUND Carney complex (CNC) is a rare multiple neoplasia syndrome with autosomal dominant inheritance. CNC is frequently misdiagnosed owing to its diverse clinical characteristics. We reported the case of a 14-year-old Saudi boy with a history of gynecomastia, Cushing syndrome, large-cell calcifying Sertoli cell tumor of the testis, and CNC. CASE REPORT The patient was referred to the pediatric endocrine clinic for evaluation of bilateral slow progressing gynecomastia for 1-year duration. His clinical examination revealed lentigenes, bilateral diffuse breast enlargement (consistent with Tanner stage III), and asymmetrical testicular enlargement, more on the left side...

Pancreatic acinar cell carcinoma is a rare type of pancreatic malignancy, which can be confused with pancreatic neuroendocrine neoplasm. Here, we describe a woman in her 80s who presented with abdominal pain and bilateral lower extremity panniculitis. She underwent surgery for a presumed diagnosis of neuroendocrine tumour with PTEN and PRKAR1A alterations; 19 months, later, a recurrence of her pancreatic malignancy was discovered. The patient underwent repeat resection and this time immunohistochemical staining confirmed the diagnosis of acinar cell carcinoma...

BACKGROUND: Several disease-causing genes have been implicated in Carney complex (CNC), including PRKAR1A , PDE8B (Phosphodiesterase 8B),and PDE11A (Phosphodiesterase 11A). The purpose of this study was to describe the clinical features of CNC in a Chinese patient and identify potential pathogenic mutations. METHODS: Genomic DNA was extracted from the peripheral venous blood obtained from one Chinese CNC family from Shandong province. Subsequently, targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate likely pathogenic mutations...

Superficial angiomyxoma is characterized as a benign, slow-growing vascular cutaneous myxoma. A 6-year-old Arab girl with no medical history presented with a vulvar tumor located on the left labia majora. The lesion was present since birth, but it had significantly increased over the last 6 months. She did not have any associated symptoms. Physical examination revealed an exophytic tumor of the left labia majora, which measured 5 cm in its major axis. Doppler ultrasound study showed a mass with abundant arterial and venous vascularization, and magnetic resonance imaging showed a highly vascular contrast-enhanced mass with well-delimited margins, which depended on the labia majora...

Fluorescence in situ hybridization (FISH) is a quick and reliable test to detect the reciprocal t(15;17)(q22;q21) translocation in acute promyeloid leukemia (APL). The typical signal pattern for positive t(15;17) is one red, one green, and two fusion when using a PML/RARA dual fusion translocation probe. However, for variant translocations leading to the fusion of a RARA gene with an alternate gene partner, a RARA break-apart probe should be used to verify the RARA rearrangement. The typical signal pattern for a positive RARA break-apart probe is one red, one green, and one fusion...

BACKGROUND/AIM: Carney complex (CNC) is a rare autosomal dominant tumor-predisposition syndrome with variable expression. Its main features are pigmentary skin lesions, soft-tissue myxomas, and endocrine overactivity or tumors. There is occasional overlap with other syndromes, and oligosymptomatic cases may escape diagnosis. This report describes the long journey of a patient until the diagnosis of CNC was finally made after a thorough diagnostic workup. CASE REPORT: The female patient was referred for treatment of a subcutaneous tumor of the lower abdomen...

AIMS: RET-fused mesenchymal neoplasms mostly affect the soft tissue of paediatric patients. Given their responsiveness to selective RET inhibitors, it remains critical to identify those extraordinary cases occurring in the visceral organs of adults. In this study, we report three RET-rearranged spindle-cell tumours occurring in the visceral organs of adults. METHODS AND RESULTS: Clinicopathological features were assessed and partner agnostic targeted next-generation sequencing on clinically validated platforms were performed...

Background: Acrodysostosis (ACRO) is a rare disorder of peripheral bone development which can be either sporadic or inherited with mutations in the PRKAR1A or PDE4D genes. The resulting phenotypical characteristics are variable and overlap with other dysostosis conditions, making diagnosis difficult without genotyping. Vertebral malformations have been reported with ACRO resulting in slowly progressive spinal cord compression leading to radiculopathy or myelopathy. Case Description: A 19-year-old female diagnosed with ACRO presented with progressively worsening lower extremity paraparesis, sensory loss, and urinary retention; she was wheelchair-bound...

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Mammalian spermatozoa are not mature after ejaculation and must undergo additional functional and structural changes within female reproductive tracts to achieve subsequent fertilization, including both capacitation and acrosome reaction (AR), which are dominated by post-translational modifications (PTMs), especially phosphorylation. However, the mechanism of protein phosphorylation during frozen-thawed sperm capacitation and AR has not been well studied. In this study, the phosphoproteomics approach was employed based on tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy to analyze frozen-thawed sperm in Ashidan yak under three sequential conditions (density gradient centrifugation-based purification, incubation in the capacitation medium and induction of AR processes by the calcium ionophore A23187 treatment)...

Genetic alterations within the cAMP/PKA pathway result in a spectrum of adrenocortical disorders. Implicated genes include GNAS, PDE8, PDE11A, PRKAR1A/B, and PRKACA. To date, somatic PRKACA mutations and germline PRKACA copy number gain have been associated with the development of cortisol-secreting adrenocortical adenomas and bilateral adrenal hyperplasia, respectively. While perturbations within the PRKAR1A gene are known to cause Carney complex, PKRACA mutations are rarely associated with an extra-adrenal phenotype...

Endogenous Cushing's syndrome is characterized by unique clinical features and comorbidities, and progress in the analysis of its genetic pathogenesis has been achieved. Moreover, prescribed glucocorticoids are also associated with exogenous Cushing's syndrome. Several animal models have been established to explore the pathophysiology and develop treatments for Cushing's syndrome. Here, we review recent studies reporting animal models of Cushing's syndrome with different features and complications induced by glucocorticoid excess...