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13 pages, 2674 KiB

Open AccessArticle

Integrated Bioinformatics Analysis Reveals Novel miRNA as Biomarkers Associated with Preeclampsia

by Mariarita Brancaccio, Caterina Giachino, Assunta Maria Iazzetta, Antonio Cordone, Elena De Marino, Ornella Affinito, Maria Vivo, Viola Calabrò, Alessandra Pollice and Tiziana Angrisano

Genes 2022, 13(10), 1781; https://doi.org/10.3390/genes13101781 - 2 Oct 2022

Cited by 4 | Viewed by 2409

Abstract

Preeclampsia is a leading cause of perinatal maternal-foetal mortality and morbidity. This study aims to identify the key microRNAs (miRNA) in preeclampsia and uncover their potential functions. We downloaded the miRNA expression profile of GSE119799 for plasma and GSE177049 for the placenta. Each [...] Read more.

Preeclampsia is a leading cause of perinatal maternal-foetal mortality and morbidity. This study aims to identify the key microRNAs (miRNA) in preeclampsia and uncover their potential functions. We downloaded the miRNA expression profile of GSE119799 for plasma and GSE177049 for the placenta. Each dataset consisted of five patients (PE) and five controls (N). From a technical point of view, we analysed the counts per million (CPM) for both datasets, highlighting 358 miRNAs in common, 78 unique for plasma and 298 unique for placenta. At the same time, we performed an expression differential analysis (|logFC| ≥ 1|and FDR ≤ 0.05) to evaluate the biological impact of the miRNAs. This approach allowed us to highlight 321 miRNAs in common between plasma and placenta, within which four were upregulated in plasma. Furthermore, the same analysis revealed five miRNAs expressed exclusively in plasma; these were also upregulated. In conclusion, the in-depth bioinformatics analysis conducted during our study will allow us, on the one hand, to verify the targets of each of the nine identified miRNAs; on the other hand, to use them both as new non-invasive biomarkers and as therapeutic targets for the development of personalised treatments. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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13 pages, 1875 KiB

Open AccessArticle

Identification of Cdk8 and Cdkn2d as New Prame-Target Genes in 2C-like Embryonic Stem Cells

by Valeria Lucci, Elena De Marino, Daniela Tagliaferri, Stefano Amente, Alessandra Pollice, Viola Calabrò, Maria Vivo, Geppino Falco and Tiziana Angrisano

Genes 2022, 13(10), 1745; https://doi.org/10.3390/genes13101745 - 27 Sep 2022

Cited by 1 | Viewed by 1907

Abstract

Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed [...] Read more.

Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame’s downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, Cdk8 and Cdkn2d, bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the Cdk8 and Cdkn2d genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of naïve pluripotency. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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27 pages, 4694 KiB

Open AccessEditor’s ChoiceArticle

Additive and Interactive Genetically Contextual Effects of HbA1c on cg19693031 Methylation in Type 2 Diabetes

by Kelsey Dawes, Willem Philibert, Benjamin Darbro, Ronald L. Simons and Robert Philibert

Genes 2022, 13(4), 683; https://doi.org/10.3390/genes13040683 - 13 Apr 2022

Cited by 6 | Viewed by 2144

Abstract

Type 2 diabetes mellitus (T2D) has a complex genetic and environmental architecture that underlies its development and clinical presentation. Despite the identification of well over a hundred genetic variants and CpG sites that associate with T2D, a robust biosignature that could be used [...] Read more.

Type 2 diabetes mellitus (T2D) has a complex genetic and environmental architecture that underlies its development and clinical presentation. Despite the identification of well over a hundred genetic variants and CpG sites that associate with T2D, a robust biosignature that could be used to prevent or forestall clinical disease has not been developed. Based on the premise that underlying genetic variation influences DNA methylation (DNAm) independently of or in combination with environmental exposures, we assessed the ability of local and distal gene x methylation (GxMeth) interactive effects to improve cg19693031 models for predicting T2D status in an African American cohort. Using genome-wide genetic data from 506 subjects, we identified a total of 1476 GxMeth terms associated with HbA1c values. The GxMeth SNPs map to biological pathways associated with the development and complications of T2D, with genetically contextual differences in methylation observed only in diabetic subjects for two GxMeth SNPs (rs2390998 AG vs. GG, p = 4.63 × 10⁻¹¹, Δβ = 13%, effect size = 0.16 [95% CI = 0.05, 0.32]; rs1074390 AA vs. GG, p = 3.93 × 10⁻⁴, Δβ = 9%, effect size = 0.38 [95% CI = 0.12, 0.56]. Using a repeated stratified k-fold cross-validation approach, a series of balanced random forest classifiers with random under-sampling were built to evaluate the addition of GxMeth terms to cg19693031 models to discriminate between normoglycemic controls versus T2D subjects. The results were compared to those obtained from models incorporating only the covariates (age, sex and BMI) and the addition of cg19693031. We found a post-pruned classifier incorporating 10 GxMeth SNPs and cg19693031 adjusted for covariates predicted the T2D status, with the AUC, sensitivity, specificity and precision of the positive target class being 0.76, 0.81, 0.70 and 0.63, respectively. Comparatively, the AUC, sensitivity, specificity and precision using the covariates and cg19693031 were only 0.71, 0.74, 0.67 and 0.59, respectively. Collectively, we demonstrate correcting for genetic confounding of cg19693031 improves its ability to detect type 2 diabetes. We conclude that an integrated genetic–epigenetic approach could inform personalized medicine programming for more effective prevention and treatment of T2D. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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17 pages, 2268 KiB

Open AccessArticle

MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case–Control Study

by Salwa Faisal, Eman A. Toraih, Lina M. Atef, Ranya Hassan, Marwa M. Fouad, Essam Al Ageeli, Manal S. Fawzy and Hussein Abdelaziz Abdalla

Genes 2022, 13(3), 505; https://doi.org/10.3390/genes13030505 - 12 Mar 2022

Cited by 4 | Viewed by 2607

Abstract

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using [...] Read more.

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using Real-Time qPCR. We also tested its association with different rs4284505A>G genotypes (based on TaqMan allelic discrimination PCR) and the available clinical data. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each genetic association model. The upregulation of miR-17 was observed in the serum of patients with alopecia compared to controls (p-value = 0.004). The ROC curve showed high diagnostic performance of miR-17 in differentiating between patients and controls (AUC = 0.85, p-value < 0.001). rs4284505*A/G heterozygotes were more susceptible to the disease (OR = 1.57, 95% CI = 1.01–2.45) under the over-dominant model. Interestingly, patients with the rs4284505*G/G genotype had a higher level of miR-17 than those with the A/A and A/G genotypes. The G/G genotype was associated with the severe phenotype (p-value = 0.038). A/G carriers were the youngest (p-value < 0.001), had more frequent scalp infection (p-value = 0.006), exhibited the worst dermatology life quality index score (p-value = 0.037), and responded less to treatment (p-value = 0.033). In conclusion, MIR17HG expression and the rs4284505 variant were significantly associated with AA and could play a role in pathogenesis and phenotype in the Egyptian population. Further multi-center studies in other ethnicities are warranted to replicate the findings. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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12 pages, 1814 KiB

Open AccessArticle

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

by Omar Andrés Bravo-Gutiérrez, Ramcés Falfán-Valencia, Alejandra Ramírez-Venegas, Raúl H. Sansores, Rafael de Jesús Hernández-Zenteno, Andrea Hernández-Pérez, Leonor García-Gómez, Jennifer Osio-Echánove, Edgar Abarca-Rojano and Gloria Pérez-Rubio

Genes 2021, 12(8), 1276; https://doi.org/10.3390/genes12081276 - 20 Aug 2021

Cited by 3 | Viewed by 3579

Abstract

Tobacco smoking results in a multifactorial disease involving environmental and genetic factors; epigenome-wide association studies (EWAS) show changes in DNA methylation levels due to cigarette consumption, partially reversible upon tobacco smoking cessation. Therefore, methylation levels could predict smoking status. This study aimed to [...] Read more.

Tobacco smoking results in a multifactorial disease involving environmental and genetic factors; epigenome-wide association studies (EWAS) show changes in DNA methylation levels due to cigarette consumption, partially reversible upon tobacco smoking cessation. Therefore, methylation levels could predict smoking status. This study aimed to evaluate the DNA methylation level of cg05575921 (AHRR) and cg23771366 (PRSS23) and their correlation with lung function variables, cigarette consumption, and nicotine addiction in the Mexican smoking population. We included 114 non-smokers (NS) and 102 current tobacco smokers (TS); we then further subclassified them as heavy smokers (HS) (n = 53) and light smokers (LS) (n = 49). We used restriction enzymes (MspI/HpaII) and qPCR to determine the DNA methylation level. We observed significant hypomethylation of cg05575921 in smokers compared to NS (p = 0.003); further analysis found a difference between HS and NS (p = 0.02). We did not observe differences between other groups or a positive correlation between methylation levels and age, BMI, cigarette consumption, nicotine addiction, or lung function. In conclusion, the cg05575921 site of AHRR is significantly hypomethylated in Mexican smokers, especially in HS (≥20 cigarettes per day). Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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19 pages, 1681 KiB

Open AccessArticle

Analysis of a Set of KDM5C Regulatory Genes Mutated in Neurodevelopmental Disorders Identifies Temporal Coexpression Brain Signatures

by Loredana Poeta, Agnese Padula, Maria Brigida Lioi, Hans van Bokhoven and Maria Giuseppina Miano

Genes 2021, 12(7), 1088; https://doi.org/10.3390/genes12071088 - 18 Jul 2021

Cited by 16 | Viewed by 3948

Abstract

Dysregulation of transcriptional pathways is observed in multiple forms of neurodevelopmental disorders (NDDs), such as intellectual disability (ID), epilepsy and autism spectrum disorder (ASD). We previously demonstrated that the NDD genes encoding lysine-specific demethylase 5C (KDM5C) and its transcriptional regulators Aristaless [...] Read more.

Dysregulation of transcriptional pathways is observed in multiple forms of neurodevelopmental disorders (NDDs), such as intellectual disability (ID), epilepsy and autism spectrum disorder (ASD). We previously demonstrated that the NDD genes encoding lysine-specific demethylase 5C (KDM5C) and its transcriptional regulators Aristaless related-homeobox (ARX), PHD Finger Protein 8 (PHF8) and Zinc Finger Protein 711 (ZNF711) are functionally connected. Here, we show their relation to each other with respect to the expression levels in human and mouse datasets and in vivo mouse analysis indicating that the coexpression of these syntenic X-chromosomal genes is temporally regulated in brain areas and cellular sub-types. In co-immunoprecipitation assays, we found that the homeotic transcription factor ARX interacts with the histone demethylase PHF8, indicating that this transcriptional axis is highly intersected. Furthermore, the functional impact of pathogenic mutations of ARX, KDM5C, PHF8 and ZNF711 was tested in lymphoblastoid cell lines (LCLs) derived from children with varying levels of syndromic ID establishing the direct correlation between defects in the KDM5C-H3K4me3 pathway and ID severity. These findings reveal novel insights into epigenetic processes underpinning NDD pathogenesis and provide new avenues for assessing developmental timing and critical windows for potential treatments. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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15 pages, 2184 KiB

Open AccessArticle

DNA Methylation of Human Choline Kinase Alpha Promoter-Associated CpG Islands in MCF-7 Cells

by Siti Aisyah Faten Mohamed Sa’dom, Sweta Raikundalia, Shaharum Shamsuddin, Wei Cun See Too and Ling Ling Few

Genes 2021, 12(6), 853; https://doi.org/10.3390/genes12060853 - 1 Jun 2021

Cited by 1 | Viewed by 3266

Abstract

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. [...] Read more.

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between –225 and –56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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7 pages, 2206 KiB

Open AccessArticle

Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line

by Lama Hamadneh, Lara Al-Lakkis, Ala A. Alhusban, Shahd Tarawneh, Bashaer Abu-Irmaileh, Sokiyna Albustanji and Abdel Qader Al-Bawab

Genes 2021, 12(5), 777; https://doi.org/10.3390/genes12050777 - 19 May 2021

Cited by 18 | Viewed by 3390

Abstract

Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH [...] Read more.

Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH gene expression and lactate concentrations in the culture media during tamoxifen resistance development in the MCF-7 cell line, and examined LDHB promoter methylation levels. An upregulation of 2.9 times of LDHB gene expression was observed around the IC50 concentration of tamoxifen in treated cells, while fluctuation in LDHA gene expression levels was found. Furthermore, morphological changes in the cell shape accompanied the changes in gene expression. Bisulfate treatment followed by sequencing of the LDHB promoter was performed to track any change in methylation levels; hypomethylation of CpG areas was found, suggesting that gene expression upregulation could be due to methylation level changes. Changes in LDHA and LDHB gene expression were correlated with the increase in lactate concentration in the culture media of treated MCF-7 cells. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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12 pages, 1555 KiB

Open AccessArticle

Association Study of SLC6A4 (5-HTTLPR) Polymorphism and Its Promoter Methylation with Rehabilitation Outcome in Patients with Subacute Stroke

by Massimo Santoro, Mariacristina Siotto, Marco Germanotta, Alessia Mastrorosa, Dionysia Papadopoulou and Irene Aprile

Genes 2021, 12(4), 579; https://doi.org/10.3390/genes12040579 - 16 Apr 2021

Cited by 7 | Viewed by 2643

Abstract

Recently it has been suggested that serotonin transporter (SLC6A4) and its 5HTTLPR polymorphism could be involved in post stroke recovery. Here, we characterized the methylation profile of two different CpG islands within the SLC6A4 promoter region in the whole blood of [...] Read more.

Recently it has been suggested that serotonin transporter (SLC6A4) and its 5HTTLPR polymorphism could be involved in post stroke recovery. Here, we characterized the methylation profile of two different CpG islands within the SLC6A4 promoter region in the whole blood of 50 patients with subacute stroke before and after a six-week rehabilitation treatment. These patients were genotyped for 5HTTLPR polymorphism identifying patients on the basis of short (S) and L (L) alleles: 17 patients LL, 22 patients LS and 11 patients SS. At baseline, all CpG sites for both CpG islands displayed a heterogeneous methylation percentage that were not influenced by the different genotypes. After rehabilitation, we found a significant variation in the methylation levels (increase/decrease) in the specific CpG sites of both CpG islands. The statistical analysis showed a significant relationship between the LL, LS and SS alleles and the outcome of the rehabilitation intervention (χ² (2,50) = 6.395, p = 0.041). Specifically, we found a significant difference between patients with or without a favorable outcome in the LL (11.1% with a favorable outcome) and in the SS (54.4% with a favorable outcome) groups. Our data suggest that 5-HTTLPR polymorphisms and SLC6A4 promoter methylation may be employed as a non-invasive biological marker of recovery in patients with stroke undergoing rehabilitation. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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Review

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14 pages, 652 KiB

Open AccessReview

Understanding the Roles of the NSD Protein Methyltransferases in Head and Neck Squamous Cell Carcinoma

by Madhavi Murali and Vassiliki Saloura

Genes 2022, 13(11), 2013; https://doi.org/10.3390/genes13112013 - 2 Nov 2022

Cited by 2 | Viewed by 2233

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent non-skin cancer in the world. While immunotherapy has revolutionized the standard of care treatment in patients with recurrent/metastatic HNSCC, more than 70% of patients do not respond to this treatment, making [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent non-skin cancer in the world. While immunotherapy has revolutionized the standard of care treatment in patients with recurrent/metastatic HNSCC, more than 70% of patients do not respond to this treatment, making the identification of novel therapeutic targets urgent. Recently, research endeavors have focused on how epigenetic modifications may affect tumor initiation and progression of HNSCC. The nuclear receptor binding SET domain (NSD) family of protein methyltransferases NSD1-NSD3 is of particular interest for HNSCC, with NSD1 and NSD3 being amongst the most commonly mutated or amplified genes respectively in HNSCC. Preclinical studies have identified both oncogenic and tumor-suppressing properties across NSD1, NSD2, and NSD3 within the context of HNSCC. The purpose of this review is to provide a better understanding of the contribution of the NSD family of protein methyltransferases to the pathogenesis of HNSCC, underscoring their promise as novel therapeutic targets in this devastating disease. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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15 pages, 313 KiB

Open AccessReview

The Role of Genetic Pathways in the Development of Chemoradiation Resistance in Nasopharyngeal Carcinoma (NPC) Patients

by Norhafiza Mat Lazim, Che Ismail Che Lah, Wan Khairunnisa Wan Juhari, Sarina Sulong, Bin Alwi Zilfalil and Baharudin Abdullah

Genes 2021, 12(11), 1835; https://doi.org/10.3390/genes12111835 - 21 Nov 2021

Cited by 7 | Viewed by 3161

Abstract

Management of nasopharyngeal carcinoma (NPC) remains elusive despite new developments and advancement that has been made in the current management approaches. A patient’s survival and prognosis remain dismal especially for a late-stage disease. This is highly attribute to the chemoradiation resistance. Arrays of [...] Read more.

Management of nasopharyngeal carcinoma (NPC) remains elusive despite new developments and advancement that has been made in the current management approaches. A patient’s survival and prognosis remain dismal especially for a late-stage disease. This is highly attribute to the chemoradiation resistance. Arrays of genes and molecular mechanisms underlie the development of chemoradiation resistance in NPC. Imperatively, unravelling the true pathogenesis of chemoradiation resistance is crucial as these significant proteins and genes can be modulated to produce an effective therapeutic target. It is pivotal to identify the chemoradiation resistance at the very beginning in order to combat the chemoradiation resistance efficiently. Intense research in the genetic ecosphere is critical, as the discovery and development of novel therapeutic targets can be used for screening, diagnosis, and treating the chemoradiation resistance aggressively. This will escalate the management trajectory of NPC patients. This article highlights the significance of genetic and molecular factors that play critical roles in the chemoradiation resistance and how these factors may be modified for next-generation targeted therapy products. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

15 pages, 798 KiB

Open AccessReview

Epigenetic Changes Induced by Maternal Factors during Fetal Life: Implication for Type 1 Diabetes

by Ilaria Barchetta, Jeanette Arvastsson, Luis Sarmiento and Corrado M. Cilio

Genes 2021, 12(6), 887; https://doi.org/10.3390/genes12060887 - 8 Jun 2021

Cited by 5 | Viewed by 3698

Abstract

Organ-specific autoimmune diseases, such as type 1 diabetes, are believed to result from T-cell-mediated damage of the target tissue. The immune-mediated tissue injury, in turn, is known to depend on complex interactions between genetic and environmental factors. Nevertheless, the mechanisms whereby environmental factors [...] Read more.

Organ-specific autoimmune diseases, such as type 1 diabetes, are believed to result from T-cell-mediated damage of the target tissue. The immune-mediated tissue injury, in turn, is known to depend on complex interactions between genetic and environmental factors. Nevertheless, the mechanisms whereby environmental factors contribute to the pathogenesis of autoimmune diseases remain elusive and represent a major untapped target to develop novel strategies for disease prevention. Given the impact of the early environment on the developing immune system, epigenetic changes induced by maternal factors during fetal life have been linked to a likelihood of developing an autoimmune disease later in life. In humans, DNA methylation is the epigenetic mechanism most extensively investigated. This review provides an overview of the critical role of DNA methylation changes induced by prenatal maternal conditions contributing to the increased risk of immune-mediated diseases on the offspring, with a particular focus on T1D. A deeper understanding of epigenetic alterations induced by environmental stressors during fetal life may be pivotal for developing targeted prevention strategies of type 1 diabetes by modifying the maternal environment. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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7 pages, 2449 KiB

Open AccessBrief Report

BRCA1/2 NGS Somatic Testing in Clinical Practice: A Short Report

by Francesco Pepe, Pasquale Pisapia, Gianluca Russo, Mariantonia Nacchio, Pierlorenzo Pallante, Elena Vigliar, Carmine De Angelis, Luigi Insabato, Claudio Bellevicine, Sabino De Placido, Giancarlo Troncone and Umberto Malapelle

Genes 2021, 12(12), 1917; https://doi.org/10.3390/genes12121917 - 28 Nov 2021

Cited by 4 | Viewed by 2774

Abstract

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of all ovarian carcinomas. HGSOC harboring BRCA1/2 germline or somatic mutations are sensitive to the poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi). Therefore, detecting these mutations is crucial to identifying patients for [...] Read more.

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of all ovarian carcinomas. HGSOC harboring BRCA1/2 germline or somatic mutations are sensitive to the poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi). Therefore, detecting these mutations is crucial to identifying patients for PARPi-targeted treatment. In the clinical setting, next generation sequencing (NGS) has proven to be a reliable diagnostic approach BRCA1/2 molecular evaluation. Here, we review the results of our BRCA1/2 NGS analysis obtained in a year and a half of diagnostic routine practice. BRCA1/2 molecular NGS records of HGSOC patients were retrieved from our institutional archive covering the period from January 2020 to September 2021. NGS analysis was performed on the Ion S5™ System (Thermo Fisher Scientific, Waltham, MA, USA) with the Oncomine™ BRCA Research Assay panel (Thermo Fisher Scientific). Variants were classified as pathogenic or likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics by using the inspection of Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) and ClinVar (NCBI) databases. Sixty-five HGSOC patient samples were successfully analyzed. Overall, 11 (16.9%) out of 65 cases harbored a pathogenic alteration in BRCA1/2, in particular, six BRCA1 and five BRCA2 pathogenic variations. This study confirms the efficiency and high sensitivity of NGS analysis in detecting BRCA1/2 germline or somatic variations in patients with HGSOC. Full article

(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)

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