scholarly journals Molecular genetic insights into sporadic primary hyperparathyroidism

2019 ◽  
Vol 26 (2) ◽  
pp. R53-R72 ◽  
Author(s):  
Kelly Brewer ◽  
Jessica Costa-Guda ◽  
Andrew Arnold
Keyword(s):  
Primary Hyperparathyroidism ◽  
Molecular Genetic ◽  
Suppressor Gene ◽  
Tumor Formation ◽  
Driver Genes ◽  
Genetic Abnormalities ◽  
Sporadic Primary Hyperparathyroidism ◽  
Parathyroid Hormone Release ◽  
Pathogenic Process

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by dysregulation of parathyroid hormone release. The large majority of PHPT cases are attributable to sporadic, single-gland parathyroid adenoma, in which MEN1 and CCND1/cyclin D1 are the most well-established drivers of tumorigenesis. Sporadic parathyroid carcinoma, which appears to mostly arise through molecular pathways distinct from those causing benign parathyroid tumors, is rare and is most frequently driven by mutational inactivation of the CDC73 (HRPT2) tumor suppressor gene. Targeted investigation of suspected tumor driver genes, as well as unbiased whole-genome or exome sequencing of small cohorts, have revealed additional novel candidate tumor genes in sporadic parathyroid neoplasia, generally at modest or low mutational frequencies consistent with marked molecular genetic heterogeneity from tumor to tumor. The ability of these additional candidates to participate in the pathogenic process of driving parathyroid tumorigenesis in vivo largely remains to be demonstrated experimentally. This review will summarize the molecular genetic abnormalities identified to date in sporadic PHPT and discuss the strength of evidence for their proposed roles in parathyroid tumor formation.

NIMG-58. CANONICAL CORRELATION ANALYSIS IN GLIOBLASTOMA REVEALS ASSOCIATIONS BETWEEN EXPRESSION OF RADIOMIC SIGNATURES AND GENOMICS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi142-vi142
Author(s):  
Jun Guo ◽  
Anahita Fathi Kazerooni ◽  
Hamed Akbari ◽  
Erik Toorens ◽  
Chiharu Sako ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Canonical Correlation Analysis ◽  
Canonical Correlation ◽  
Molecular Genetic ◽  
Tumor Formation ◽  
Imaging Features ◽  
Genetic Characteristics ◽  
Molecular Alterations ◽  
Cellular Density

Abstract PURPOSE Understanding the molecular underpinnings of imaging signatures of glioblastoma can provide insights into the biologic basis of tumor formation and progression as well as in vivo surrogate markers of molecular events driving the tumor’s phenotype. Through machine learning (ML), this study demonstrates that distinct imaging subtypes of glioblastoma are related to specific molecular alterations. METHODS Pre-operative multi-parametric MRI (T1, T2, T1CE, T2-FLAIR, DSC-MRI, DTI-MRI) of 669 IDH-wildtype subjects with glioblastoma were retrospectively collected and radiomic features, including descriptors of morphology, intensity, histogram, and texture, were extracted. Imaging subtypes were identified by a feature selection and clustering approach. Genomic markers, obtained using next generation sequencing (NGS) panel of 27 key glioblastoma genes, were available in 358/669 patients. Canonical correlation analysis (CCA) was conducted within each imaging subtype between the selected imaging features and genetic variables to seek maximum correlations between combinations of variables in imaging and genomic sets, and hence elucidate the molecular drivers of respective subtypes. RESULTS Three distinct imaging subtypes were identified by clustering on 50 selected features, representing characteristics of morphology, tumor neo-angiogenesis (DSC-derived features), and cellular density (DTI-derived features). These subtypes yielded differentiable overall survival based on Kaplan-Meier analysis. The canonical coefficients of each subtype revealed the distinction of the underlying genomic characteristics: one exhibited frequently mutated [ARID2, NTRK1], another subtype showed increased frequency of mutation in [ATRX, EGFR, PIK3R1], while the third was associated with all these genes and [NF1, PIK3CA, RB1], additionally. CONCLUSION We derived three distinct radiomic MRI subtypes for glioblastoma that highly correlate with the patients' survival and molecular genetic characteristics. Investigating the relationship between imaging and genomic information may enable identification of molecularly- and phenotypically-consistent tumor subtypes, which would offer non-invasive approaches for characterizing heterogeneity of glioblastoma, further facilitating patient stratification and treatment planning.

CDC73 mutations in young patients with primary hyperparathyroidism: A description of two clinical cases

2016 ◽  
Vol 88 (10) ◽  
pp. 57-62 ◽  
Author(s):  
E O Mamedova ◽  
N G Mokrysheva ◽  
E A Pigarova ◽  
E G Przhiyalkovskaya ◽  
I A Voronkova ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Carcinoma ◽  
Molecular Genetic ◽  
Young Patients ◽  
Suppressor Gene ◽  
Young Female ◽  
Personal Genome ◽  
Nonsense Mutations ◽  
Thermo Fisher Scientific ◽  
Clinical Cases

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific — Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

scholarly journals HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Lei ◽  
Wen-Ting Yang ◽  
Peng-Sheng Zheng
Keyword(s):  
Cervical Cancer ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Tumor Formation ◽  
Cervical Cancer Cell ◽  
Cancer Cell Growth ◽  
Bioinformatics Analyses

AbstractHomeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/β-catenin signaling pathway by direct transcriptional repression of β-catenin. Furthermore, β-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed β-catenin and subsequently inactivated the Wnt/β-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.

scholarly journals Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes

2021 ◽  
Vol 10 (5) ◽  
pp. 1759-1771
Author(s):  
Xuefen Yan ◽  
Lu Wang ◽  
Lingxu Jiang ◽  
Yingwan Luo ◽  
Peipei Lin ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Myelodysplastic Syndromes ◽  
Molecular Genetic ◽  
Chinese Patients ◽  
Genetic Abnormalities

scholarly journals Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma

2021 ◽  
Author(s):  
Xiuming Liu ◽  
Xiaofeng Li ◽  
Jianchang Li
Keyword(s):  
Cell Viability ◽  
Antisense Rna ◽  
Tumor Formation ◽  
Retinoblastoma Cell ◽  
Non Coding Rna ◽  
High Incidence ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Common Malignancy

AbstractRetinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.

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