scholarly journals Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 441 ◽  
Author(s):  
Simona Coco ◽  
Silvia Bonfiglio ◽  
Davide Cittaro ◽  
Irene Vanni ◽  
Marco Mora ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Smoking Habit ◽  
Cancer Control ◽  
Sequencing Analysis ◽  
Multiple Cancer ◽  
Germline Variants ◽  
Whole Exome

Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result of harboring rare variants. Sixty patients with LC with previous BC (the study population; SP) and 53 women with either BC or LC and no secondary cancer (control population; CP) were enrolled. Whole exome sequencing was performed in both tumors and unaffected tissues from 28/60 SP patients, and in germline DNA from 32/53 CP. Candidate genes were validated in the remaining individuals from both populations. We found two main mutational signature profiles: S1 (C>T) in all BCs and 16/28 LCs, and S2 (C>A) which is strongly associated with smoking, in 12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified 248 genes. Validation confirmed GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk.

scholarly journals Lung cancer predisposition in women with previous breast cancer identified by whole exome sequencing

2018 ◽  
Vol 29 ◽  
pp. viii674
Author(s):  
F. Grossi ◽  
C. Genova ◽  
D. Cittaro ◽  
S. Bonfiglio ◽  
S. Boccardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Cancer Predisposition ◽  
Whole Exome

scholarly journals Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures

2021 ◽  
Author(s):  
Adam L. Numis ◽  
Gilberto da Gente ◽  
Elliott H. Sherr ◽  
Hannah C. Glass
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
List Type ◽  
Sequencing Analysis ◽  
Neonatal Seizures ◽  
Pathogenic Variants ◽  
Targeted Analysis ◽  
Whole Exome ◽  
Epilepsy Gene

Abstract Background The contribution of pathogenic gene variants with development of epilepsy after acute symptomatic neonatal seizures is not known. Methods Case–control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We performed whole-exome sequencing (WES) and identified pathogenic de novo, transmitted, and non-transmitted variants from established and candidate epilepsy association genes and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). We analyzed variants throughout the exome to evaluate for differential enrichment of functional properties using exploratory KEGG searches. Results Querying 200 established and candidate epilepsy genes, pathogenic variants were identified in 5 children with post-neonatal epilepsy yet in only 1 child without subsequent epilepsy. There was no difference in the number of trios with non-transmitted pathogenic variants in epilepsy or CAD genes. An exploratory KEGG analysis demonstrated a relative enrichment in cell death pathways in children without subsequent epilepsy. Conclusions In this pilot study, children with epilepsy after acute symptomatic neonatal seizures had a higher prevalence of coding variants with a targeted epilepsy gene sequencing analysis compared to those patients without subsequent epilepsy. Impact We performed whole-exome sequencing (WES) in 20 trios, including 10 children with epilepsy and 10 without epilepsy, both after acute symptomatic neonatal seizures. Children with post-neonatal epilepsy had a higher burden of pathogenic variants in epilepsy-associated genes compared to those without post-neonatal epilepsy. Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.

scholarly journals Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ege Ülgen ◽  
Özge Can ◽  
Kaya Bilguvar ◽  
Cemaliye Akyerli Boylu ◽  
Şirin Kılıçturgay Yüksel ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Analysis ◽  
Clinical Interpretation ◽  
Germline Variants ◽  
Whole Exome ◽  
Gene Level ◽  
Analysis Workflow ◽  
Tumor Mutational Burden ◽  
Diffuse Gliomas

Abstract Background In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings. Methods The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses. Using the workflow, 58 WES analyses from matched blood and tumor samples of 52 patients were analyzed: 47 primary and 11 recurrent diffuse gliomas. Results The median mean read depths were 199.88 for tumor and 110.955 for normal samples. For germline variants, a median of 22 (14–33) variants per patient was reported. There was a median of 6 (0–590) reported somatic short variants per tumor. A median of 19 (0–94) broad SCNAs and a median of 6 (0–12) gene-level SCNAs were reported per tumor. The gene with the most frequent somatic short variants was TP53 (41.38%). The most frequent chromosome-/arm-level SCNA events were chr7 amplification, chr22q loss, and chr10 loss. TMB in primary gliomas were significantly lower than in recurrent tumors (p = 0.002). MSI incidence was low (6.9%). Conclusions We demonstrate that WES can be practically and efficiently utilized for clinical analysis of individual brain tumors. The results display that NOTATES produces clinically relevant results in a concise but exhaustive manner.

scholarly journals NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Xu ◽  
Yong-Biao Zhang ◽  
Li-Jun Liang ◽  
Jia-Li Tian ◽  
Jin-Ming Lin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Sanger Sequencing ◽  
Conformational Stability ◽  
Sequencing Analysis ◽  
Large Pedigree ◽  
Whole Exome ◽  
Variant Filtering ◽  
Genetic Contributions

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. Methods We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. Results After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. Conclusions NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

scholarly journals TP53 and PTEN mutations were shared in concurrent germ cell tumor and acute megakaryoblastic leukemia

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Keiichi Akizuki ◽  
Masaaki Sekine ◽  
Yasunori Kogure ◽  
Takuro Kameda ◽  
Kotaro Shide ◽  
...  
Keyword(s):  
Germ Cell ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Germ Cell Tumor ◽  
Somatic Mutations ◽  
Cell Tumor ◽  
Sequencing Analysis ◽  
Male Adult ◽  
Clonal Relationship ◽  
Whole Exome

Abstract Background The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results Sixteen somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.

scholarly journals Ablepharon macrostomia syndrome in a Thai patient: case report and literature review

2020 ◽  
Vol 14 (2) ◽  
pp. 83-88
Author(s):  
Phawin Kor-anantakul ◽  
Kanya Suphapeetiporn ◽  
Somchit Jaruratanasirikul
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sequencing Analysis ◽  
Patient Case ◽  
Thai Patient ◽  
Labia Minora ◽  
Whole Exome ◽  
Rare Congenital Disorder

AbstractAblepharon macrostomia syndrome (AMS) is a rare congenital disorder. To our knowledge, only 20 cases have been reported to date, and all in patients from Western countries. We report a case of AMS in a Thai patient, who presented at age 3 months with severe ectropion of both upper and lower eyelids, alopecia totalis, no palpable clitoris, and hypoplasia of both labia minora and labia majora. Trio whole exome sequencing analysis was performed, which revealed a heterozygous missense c.223G>A (p.Glu75Lys) variation in TWIST2. To our knowledge, this is the first reported case of AMS in a patient from Thailand and the first reported case of AMS in Asia.

scholarly journals Whole-exome sequencing analysis on products of conception: A cohort study to evaluate clinical utility and genetic etiology for pregnancy loss

2020 ◽  
Author(s):  
Chen Zhao ◽  
Hongyan Chai ◽  
Qinghua Zhou ◽  
Jiadi Wen ◽  
Uma M. Reddy ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Utility ◽  
Pregnancy Loss ◽  
Renal Diseases ◽  
Sequencing Analysis ◽  
Genetic Etiology ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Products Of Conception

Purpose: Pregnancy loss ranging from spontaneous abortion (SAB) to stillbirth can result from monogenic causes of Mendelian inheritance. This study evaluated the clinical application of whole exome sequencing (WES) in identifying the genetic etiology for pregnancy loss. Methods: A cohort of 102 specimens from products of conception (POC) with normal karyotype and absence of pathogenic copy number variants were selected for WES. Abnormality detection rate (ADR) and variants of diagnostic value correlated with SAB and stillbirth were evaluated. Results: WES detected six pathogenic variants, 16 likely pathogenic variants, and 17 variants of uncertain significance favor pathogenic (VUSfp) from this cohort. The ADR for pathogenic and likely pathogenic variants was 22% and reached 35% with the inclusion of VUSfp. The ADRs of SAB and stillbirth were 36% and 33%, respectively. Affected genes included those associated with multi-system abnormalities, neurodevelopmental disorders, cardiac anomalies, skeletal dysplasia, metabolic disorders and renal diseases. Conclusion: These results supported the clinical utility of WES for detecting monogenic etiology of pregnancy loss. The identification of disease associated variants provided information for follow-up genetic counseling of recurrence risk and management of subsequent pregnancies. Discovery of novel variants could provide insight for underlying molecular mechanisms causing fetal death.

Sign in / Sign up

Export Citation Format

Share Document