Genomic analysis-integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway

Background. Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortality in China with increasing incidence. This study is designed to explore early genetic changes implicated in HCC tumorigenesis and progression by whole-exome sequencing. Methods. We firstly sequenced the whole exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood samples, followed by gene ontological analysis and pathway analysis of the single-nucleotide variants discovered. Then, the mutations of high frequency were further confirmed by Sanger sequencing. Results. We identified a mutational signature of dominant T:A>A:T transversion in early HCC and significantly enriched pathways including ECM-receptor interaction, axon guidance, and focal adhesion and enriched biological processes containing cell adhesion, axon guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A, DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions. This study reveals a mutational profile and a distinct mutation signature of T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our understanding of genetic characteristics of the early-stage HCC.

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Near universal detection of alterations inCTNNB1and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis

Genes Chromosomes and Cancer ◽

10.1002/gcc.22272 ◽

2015 ◽

Vol 54 (10) ◽

pp. 606-615 ◽

Cited By ~ 64

Author(s):

Aimee M. Crago ◽

Juliann Chmielecki ◽

Mara Rosenberg ◽

Rachael O'Connor ◽

Caitlin Byrne ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Wnt Pathway ◽

Genomic Analysis ◽

Whole Exome ◽

Universal Detection

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Identification of genetic mutations related to invasion and metastasis of acral melanoma via whole‐exome sequencing

The Journal of Dermatology ◽

10.1111/1346-8138.15841 ◽

2021 ◽

Author(s):

Youngkyoung Lim ◽

Dong‐Youn Lee

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genetic Mutations ◽

Invasion And Metastasis ◽

Acral Melanoma ◽

Whole Exome

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Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome

Journal of Molecular Medicine ◽

10.1007/s00109-021-02112-z ◽

2021 ◽

Author(s):

Yan Zhao ◽

Lee-kai Wang ◽

Ascia Eskin ◽

Xuedong Kang ◽

Viviana M. Fajardo ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genomic Analysis ◽

Genetic Contribution ◽

Endocardial Fibroelastosis ◽

Rna Seq ◽

Live Births ◽

Alström Syndrome ◽

Whole Exome ◽

Alstrom Syndrome

Abstract Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband’s dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFβ signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. Key message Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications.

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Genetic mutations and signatures in lung cancer – findings from a whole exome sequencing platform

Lung Cancer ◽

10.1016/s0169-5002(21)00200-2 ◽

2021 ◽

Vol 156 ◽

pp. S1

Author(s):

Sanjay Dutta ◽

Paul Leo ◽

Arutha Kulasinghe ◽

James Monkman ◽

David Pennisi ◽

...

Keyword(s):

Lung Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genetic Mutations ◽

Sequencing Platform ◽

Whole Exome

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Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.645501 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yang Liu ◽

Jin-Jin Zhang ◽

Shun-Yu Piao ◽

Ren-Juan Shen ◽

Ya Ma ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Chinese Population ◽

High Myopia ◽

Northwest China ◽

Genetic Mutations ◽

1000 Genomes ◽

Reference Information ◽

Whole Exome ◽

Exome Aggregation Consortium

High myopia (HM) is one of the leading causes of visual impairment worldwide. In order to expand the myopia gene spectrum in the Chinese population, we investigated genetic mutations in a cohort of 27 families with HM from Northwest China by using whole-exome sequencing (WES). Genetic variations were filtered using bioinformatics tools and cosegregation analysis. A total of 201 candidate mutations were detected, and 139 were cosegregated with the disease in the families. Multistep analysis revealed four missense variants in four unrelated families, including c.904C>T (p.R302C) in CSMD1, c.860G>A (p.R287H) in PARP8, c.G848A (p.G283D) in ADAMTSL1, and c.686A>G (p.H229R) in FNDC3B. These mutations were rare or absent in the Exome Aggregation Consortium (ExAC), 1000 Genomes Project, and Genome Aggregation Database (gnomAD), indicating that they are new candidate disease-causing genes. Our findings not only expand the myopia gene spectrum but also provide reference information for further genetic study of heritable HM.

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Investigation of Genetic Mutations in High-risk and Low-risk Basal Cell Carcinoma in a Non-Caucasian Population by Whole Exome Sequencing

Acta Dermato Venereologica ◽

10.2340/00015555-3820 ◽

2021 ◽

pp. 0

Author(s):

H Kim ◽

M Lee ◽

Y Lee ◽

D Yu

Keyword(s):

High Risk ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Basal Cell ◽

Caucasian Population ◽

Low Risk ◽

Genetic Mutations ◽

Whole Exome

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Whole Exome Sequencing in Idiopathic Short Stature: Rare Mutations Affecting Growth

10.21203/rs.2.22066/v1 ◽

2020 ◽

Author(s):

Nami Mohammadian Khonsari ◽

Shahab Noorian ◽

Farzaneh Rohani ◽

Sharham Savad ◽

Kourosh Kabir ◽

...

Keyword(s):

Short Stature ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Correct Diagnosis ◽

Idiopathic Short Stature ◽

Genetic Mutations ◽

The Past ◽

Rare Mutations ◽

Whole Exome ◽

Directing Attention

Abstract Introduction Evaluation of short stature is a challenge for pediatricians and in the process, idiopathic short stature (ISS) is an often diagnosis of exclusion. Non-pathogenetic mutations affecting height may present with phenotypes similar to the pathogenetic mutations. In this study, we aim to identify the underlying genetic cause of short stature in patients diagnosed with ISS and investigate potential treatments for them. Materials and Methods We identified 14 children in our practice who were under the age of 15 and were initially labelled as ISS. Then, we evaluated their plasma whole-exome sequencing (WES). Results Out of the 14 patients assessed with WES, five had normal results and correctly diagnosed with ISS. However, four of them had rare mutations that have not been extensively studied in the past. Due to the functions of these mutated genes and our patients’ phenotypes, we suspect that these mutations played a role in the short stature. Out of the remaining five patients, four had genetic mutations known to cause short stature and one had a mutation that was known not to affect height. Conclusion In patients who are initially diagnosed with ISS, WES can help to identify rare mutations that may play a role in short stature. Directing attention to these genes, may help with the correct diagnosis and choosing proper treatment for the patients.

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Single Nucleotide Variants in A Family of Monozygotic Twins Discordant for the Phenotype Congenital Megaureter: A Genomic Analysis

The Open Urology & Nephrology Journal ◽

10.2174/1874303x01710010011 ◽

2017 ◽

Vol 10 (1) ◽

pp. 11-19

Author(s):

Augusto C. Soares dos Santos Junior ◽

Luciana B. Rodrigues ◽

Raony G. Corrêa Do Carmo Lisboa Cardenas ◽

Patricia G.P. Couto ◽

Luiz A. Cunha de Marco ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Monozygotic Twins ◽

Genomic Analysis ◽

Genetic Variations ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Whole Exome ◽

Sequencing Technique ◽

Related Individuals

Introduction: Congenital megaureter constitutes the second most frequent cause of hydronephrosis in children. There is still much debate on what extent environmental or genetic factors are involved in the pathogenesis of congenital megaureter. Objectives: This study aimed at investigating a pair of monozygotic twins discordant for the expression of bilateral congenital megaureter using the whole exome sequencing technique. Methods: Peripheral blood DNA was extracted and then sequenced using the whole exome technique from a pair of twins discordant for the presence of bilateral congenital refluxing unobstructed megaureter, his parents and a set of 11 non-related individuals with confirmed diagnosis of congenital megaureter. The DNA of the set of 11 non-related individuals was pooled in three groups. The monozygotic twins and their parents had DNA samples sequenced separately. Sanger validation was performed after data was filtered. Results: In the proband were identified 256 candidate genes, including TBX3, GATA6, DHH, LDB3, and HNF1, which are expressed in the urinary tract during the embryonic period. After Sanger validation, the SNVs found in the genes TBX3, GATA6, DHH and LDB3 were not confirmed in the proband. The SNV chr17:36104650 in the HNF1b gene was confirmed in the proband, his twin brother and the mother, however was not found in the pool of 11 non-related individuals with congenital megaureter. Conclusion: Due to the possible complex causative network of genetic variations and the challenges regarding the use of the whole exome sequencing technique we could not unequivocally associate the genetic variations identified in this study with the development of the congenital megaureter.

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