Abstract 3276: Whole exome sequencing identifies significantly linked regions on multiple chromosomes in families with a history of lung cancer

Abstract Background: To understand the molecular mechanism of synchronous multifocal lung cancer (SMLC) is of great significance for the differential diagnosis of intrapulmonary metastasis (IM) and synchronous multiple primary lung cancer (SMPLC). Recently, next-generation sequencing (NGS) has become a useful tool for understanding SMLC. Case presentation: In this study, two lesions of a 61-year-old man with lung cancer were detected by whole exome sequencing (WES) and the correlation between different lesions was analyzed at the molecular level. Lesion 1 was adenocarcinoma and lesion 2 was squamous cell carcinoma. Gene mutation and copy number variation (CNV) are different in the two lesions. The genome of lesion 2 is more unstable. The clonal evolution analysis showed that there was no obvious evolutionary relationship between the two lesions, and both lesions were independent double primary lesions. Bioinformatics analysis revealed that the alternate genes of the two lesions were inconsistent in function and pathway. PCA analysis was performed using the Cancer Genome Atlas (TCGA) database and the GTEx database, and it was found that the changed genes in these two lesions were significantly separated from the control group, and the changes of TP53 and EGFR genes in the TCGA database were further described. Conclusions: These results indicate that NGS may provide new ideas for SMLC classification.

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Abstract 16468: Results of Research Genetic Testing in Pediatric Cardiomyopathy Patients Justify Broader Clinical Genetic Testing

Circulation ◽

10.1161/circ.132.suppl_3.16468 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Stephanie M Ware ◽

Steven E Lipshultz ◽

Steven D Colan ◽

Ling Shi ◽

Charles E Canter ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Risk Stratification ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Clinical Genetic ◽

Clinical Genetic Testing ◽

Whole Exome ◽

Pediatric Cardiomyopathy ◽

History Of

Introduction: Pediatric cardiomyopathies are genetically heterogeneous diseases with high risk of death or cardiac transplant. Despite progress in identifying causes, the majority of cases remain idiopathic. Currrently, genetic testing is not performed in all children with cardiomyopathy. Gene identification leads to better individual risk stratification and has the potential to stimulate the development of therapies based on the underlying mutation. The aim of this study is to identify genetic mutations in pediatric cardiomyopathy patients using whole exome sequencing. Hypothesis: Sarcomeric mutations are under-diagnosed causes of all forms of cardiomyopathy in children. Methods: Probands with cardiomyopathy were recruited from 11 institutions. Results of clinical genetic testing prior to enrollment were collected. Whole exome sequencing was performed and mutations were identified in 35 genes currently available on clinical genetic testing panels. Results: The initial 154 probands subjected to exome included 78 patients with DCM, 43 with HCM, 14 with RCM, and 19 with LVNC, mixed, or unknown types. Familial disease was present in 38% and the remainder were idiopathic. Twenty-seven percent had positive clinical genetic testing prior to enrollment. Exome testing identified mutations in 38 subjects who had not had clinical testing, increasing the cohort positive testing rate to 55% (DCM, 34.6%; HCM, 74.4%; RCM, 71.4%). Forty-five percent of subjects with no family history of disease had an identifiable mutation. Conclusions: Pediatric cardiomyopathy patients have a high incidence of mutations that can be identified by clinically available genetic testing. Lack of a family history of cardiomyopathy was not predictive of normal genetic testing. These results support the broader use of genetic testing in pediatric patients with all functional phenotypes of cardiomyopathy to identify disease causation allowing better family risk stratification.

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Mutation Profile of Tibetan Lung Cancer Revealed by Whole Exome Sequencing

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.006 ◽

2020 ◽

Vol 15 (1) ◽

pp. e10-e13

Author(s):

Xin Wang ◽

Yutian Lai ◽

Wei Dai ◽

Jintao He ◽

Guowei Che

Keyword(s):

Lung Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome ◽

Mutation Profile

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

Cancers ◽

10.3390/cancers11040441 ◽

2019 ◽

Vol 11 (4) ◽

pp. 441 ◽

Cited By ~ 1

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.

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Mutation profile of Tibetan lung cancer revealed by whole exome sequencing

Annals of Oncology ◽

10.1093/annonc/mdz238.052 ◽

2019 ◽

Vol 30 ◽

pp. v15

Author(s):

X. Wang ◽

Y. Lai ◽

G. Che ◽

F. Zhao ◽

F. Yang

Keyword(s):

Lung Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome ◽

Mutation Profile

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Low Input Whole-Exome Sequencing to Determine the Representation of the Tumor Exome in Circulating DNA of Non-Small Cell Lung Cancer Patients

PLoS ONE ◽

10.1371/journal.pone.0161012 ◽

2016 ◽

Vol 11 (8) ◽

pp. e0161012 ◽

Cited By ~ 31

Author(s):

Steffen Dietz ◽

Uwe Schirmer ◽

Clémentine Mercé ◽

Nikolas von Bubnoff ◽

Edgar Dahl ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Exome Sequencing ◽

Cancer Patients ◽

Whole Exome Sequencing ◽

Small Cell ◽

Circulating Dna ◽

Small Cell Lung ◽

Lung Cancer Patients ◽

Whole Exome

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Clinical implications of identifying pathogenic variants in aortic dissection patients with whole exome sequencing

10.1101/497917 ◽

2018 ◽

Author(s):

Brooke N. Wolford ◽

Whitney E. Hornsby

Keyword(s):

Family History ◽

Aortic Dissection ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Family Members ◽

Aortic Disease ◽

Thoracic Aortic Dissection ◽

Pathogenic Variants ◽

Whole Exome ◽

History Of

ABSTRACTBackgroundThoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or their family members.MethodsWe performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity.ResultsTwenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 vs. 57 years), higher rates of root aneurysm (54% vs. 30%), less hypertension (15% vs. 57%), lower rates of smoking (19% vs. 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed significant risk factors associated with pathogenic variants are age <50 [odds ratio (OR) = 5.5; 95% CI: 1.6-19.7], no history of hypertension (OR=5.6; 95% CI: 1.4-22.3) and family history of aortic disease (mother: OR=5.7; 95% CI: 1.4-22.3, siblings: OR=5.1; 95% CI 1.1-23.9, children: OR=6.0; 95% CI: 1.4-26.7).ConclusionsClinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset of aortic dissection <50 years old, family history of aortic disease, and no history of hypertension.

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Case Report: Identification of a de novo Microdeletion 1q44 in a Patient With Seizures and Developmental Delay

Frontiers in Genetics ◽

10.3389/fgene.2021.648351 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yiehen Tung ◽

Haiying Lu ◽

Wenxin Lin ◽

Tingting Huang ◽

Samuel Kim ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

De Novo ◽

Clinical Symptoms ◽

Karyotype Analysis ◽

Microdeletion Syndrome ◽

Phenotypic Spectrum ◽

Whole Exome ◽

Number Variation ◽

History Of

Objective: 1q44 microdeletion syndrome is difficult to diagnose due to the wide phenotypic spectrum and strong genetic heterogeneity. We explore the correlation between the chromosome microdeletions and phenotype in a child with 1q44 microdeletion syndrome, we collected the clinical features of the patient and combined them with adjacent copy number variation (CNV) regions previously reported.Methods: We collected the full medical history of the patient and summarized her clinical symptoms. Whole-exome sequencing (WES) and CapCNV analysis were performed with DNA extracted from both the patient's and her parents' peripheral blood samples. Fluorescent quantitative PCR (q-PCR) was performed for the use of verification to the CNV regions.Results: A 28.7 KB microdeletion was detected in the 1q44 region by whole-exome sequencing and low-depth whole-genome sequencing. The deleted region included the genes COX20 and HNRNPU. As verification, karyotype analysis showed no abnormality, and the results of qPCR were consistent with that of whole-exome sequencing and CapCNV analysis.Conclusion: The patient was diagnosed with 1q44 microdeletion syndrome with clinical and genetic analysis. Analyzing both whole-exome sequencing and CapCNV analysis can not only improve the diagnostic rate of clinically suspected syndromes that present with intellectual disability (ID) and multiple malformations but also support further study of the correlation between CNVs and clinical phenotypes. This study lays the foundation for the further study of the pathogenesis of complex diseases.

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