scholarly journals Somatic Mutations in H-RAS in Sporadic Pheochromocytoma and Paraganglioma Identified by Exome Sequencing

2013 ◽  
Vol 98 (7) ◽  
pp. E1266-E1271 ◽  
Author(s):  
Joakim Crona ◽  
Alberto Delgado Verdugo ◽  
Rajani Maharjan ◽  
Peter Stålberg ◽  
Dan Granberg ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Signaling Pathway ◽  
Somatic Mutations ◽  
Predictive Marker ◽  
Erk Signaling ◽  
Illumina Hiseq ◽  
Ras Mutations ◽  
Mutational Status ◽  
Whole Exome ◽  
Sporadic Pheochromocytoma

Context: Up to 60% of pheochromocytoma (PCC) and paraganglioma (PGL) are associated with either somatic or germline mutations in established PCC and PGL susceptibility loci. Most unexplained cases are characterized by an increased activity of the RAS/RAF/ERK signaling pathway. Mutations in RAS subtypes H, K, and N are common in human cancers; however, previous studies have been inconsistent regarding the mutational status of RAS in PCC and PGL. Objectives: The aim of this study was to identify novel disease causing genes in PCC and PGL tumors. Design, setting, and participants: Four benign and sporadic PCC and PGL tumors were subjected to whole exome sequencing using the Illumina HiSeq Platform. Sequences were processed by CLC genomics 4.9 bioinformatics software and the acquired list of genetic variants was filtered against the Catalogue of Somatic Mutations in Cancer database. Findings were validated in an additional 78 PCC and PGL tumor lesions. Results: Exome sequencing identified 2 cases with somatic mutations in the H-RAS. In total, 6.9% (n = 4/58) of tumors negative for mutations in major PCC and PGL loci had mutations in H-RAS: G13R, Q61K, and Q61R. There were 3 PCC and 1 PGL; all had sporadic presentation with benign tumor characteristics and substantial increases in norepinephrine and/or epinephrine. H-RAS tumors were exclusively found in male patients (P = .007). Conclusions: We identified recurrent somatic H-RAS mutations in pheochromocytoma and paraganglioma. Tumors with H-RAS mutations had activation of the RAS/RAF/ERK signaling pathway and were associated with male PCC patients having benign and sporadic disease characteristics. H-RAS could serve as a prognostic and predictive marker as well as a novel therapeutic target.

scholarly journals Germline and somatic mutations in the pathology of pineal cyst: A whole‐exome sequencing study of 93 individuals

2021 ◽  
Author(s):  
Yuanqing Yan ◽  
Rebecca Martinez ◽  
Maria N. Rasheed ◽  
Joshua Cahal ◽  
Zhen Xu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutations ◽  
Pineal Cyst ◽  
Whole Exome

Whole-exome sequencing reveals potential germline and somatic mutations in 60 malignant ovarian germ cell tumors

2021 ◽  
Author(s):  
Juan Chen ◽  
Yan Li ◽  
Jianlei Wu ◽  
Yakun Liu ◽  
Shan Kang
Keyword(s):  
Germ Cell ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Peripheral Blood ◽  
Copy Number ◽  
Somatic Mutations ◽  
Germ Cell Tumors ◽  
Germline Mutations ◽  
Deletion Region ◽  
Whole Exome

Abstract Background Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. Methods The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes corresponding to copy number alterations (CNA) deletion and duplication region, functional annotation of was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region. Results In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YST). Moreover, POU5F1 was the most significant mutated gene with mutation frequency > 10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region) was found in 2 YST and nuclear staining in 2 dysgerminomas (DG) tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I-like receptor, Toll-like receptor, NF-kappa B and Jak–STAT. KRT4, RPL14, PCSK6, PABPC3 and SARM1 mutations were detected in both peripheral blood and tumor samples. Conclusions Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

scholarly journals Whole-Exome Sequencing Identifies Somatic Mutations Associated With Mortality in Metastatic Clear Cell Kidney Carcinoma

2019 ◽  
Vol 10 ◽  
Author(s):  
Alejandro Mendoza-Alvarez ◽  
Beatriz Guillen-Guio ◽  
Adrian Baez-Ortega ◽  
Carolina Hernandez-Perez ◽  
Sita Lakhwani-Lakhwani ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutations ◽  
Clear Cell ◽  
Kidney Carcinoma ◽  
Whole Exome

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 Detection and benchmarking of somatic mutations in cancer genomes using RNA-seq data

2018 ◽  
Author(s):  
Alexandre Coudray ◽  
Anna M. Battenhouse ◽  
Philipp Bucher ◽  
Vishwanath R. Iyer
Keyword(s):  
Exome Sequencing ◽  
Somatic Mutations ◽  
Low Cost ◽  
Systematic Evaluation ◽  
Rna Seq ◽  
Whole Exome ◽  
Cancer Genomes ◽  
Additional Support ◽  
Coding Variants ◽  
Measure Gene Expression

ABSTRACTTo detect functional somatic mutations in tumor samples, whole-exome sequencing (WES) is often used for its reliability and relative low cost. RNA-seq, while generally used to measure gene expression, can potentially also be used for identification of somatic mutations. However there has been little systematic evaluation of the utility of RNA-seq for identifying somatic mutations. Here, we develop and evaluate a pipeline for processing RNA-seq data from glioblastoma multiforme (GBM) tumors in order to identify somatic mutations. The pipeline entails the use of the STAR aligner 2-pass procedure jointly with MuTect2 from GATK to detect somatic variants. Variants identified from RNA-seq data were evaluated by comparison against the COSMIC and dbSNP databases, and also compared to somatic variants identified by exome sequencing. We also estimated the putative functional impact of coding variants in the most frequently mutated genes in GBM. Interestingly, variants identified by RNA-seq alone showed better representation of GBM-related mutations cataloged by COSMIC. RNA-seq-only data substantially outperformed the ability of WES to reveal potentially new somatic mutations in known GBM-related pathways, and allowed us to build a high-quality set of somatic mutations common to exome and RNA-seq calls. Using RNA-seq data in parallel with WES data to detect somatic mutations in cancer genomes can thus broaden the scope of discoveries and lend additional support to somatic variants identified by exome sequencing alone.

scholarly journals Sequential Whole Exome Sequencing Reveals Somatic Mutations Associated with Platinum Response in NSCLC

2020 ◽  
Vol Volume 13 ◽  
pp. 6485-6496 ◽  
Author(s):  
Ao-Xiang Guo ◽  
Fan Xiao ◽  
Wei-Hua Shao ◽  
Yan Zhan ◽  
Le Zhang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutations ◽  
Whole Exome

scholarly journals Whole-exome sequencing of duodenal adenocarcinoma identifies recurrent Wnt/β-catenin signaling pathway mutations

Cancer ◽  
2016 ◽  
Vol 122 (11) ◽  
pp. 1689-1696 ◽  
Author(s):  
Wei Yuan ◽  
Zhou Zhang ◽  
Binghua Dai ◽  
Qing Wei ◽  
Jinjin Liu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Signaling Pathway ◽  
Whole Exome Sequencing ◽  
Duodenal Adenocarcinoma ◽  
Whole Exome

scholarly journals The Profile of Genetic Mutations in Papillary Thyroid Cancer Detected by Whole Exome Sequencing

2018 ◽  
Vol 50 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Yi Fang ◽  
Xiao Ma ◽  
Jing Zeng ◽  
Yanwen Jin ◽  
Yong Hu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Exome Sequencing ◽  
Papillary Thyroid Cancer ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Signal Pathways ◽  
Papillary Thyroid ◽  
Driver Genes ◽  
Mutational Status ◽  
Whole Exome

Background/Aims: The purpose of the study was to investigate the altered driver genes and signal pathways during progression of papillary thyroid cancer (PTC) via next-generation sequencing technology. Methods: The DNA samples for whole exome sequencing (WES) analyses were extracted from 11 PTC tissues and adjacent normal tissues samples. Direct Sanger sequencing was applied to validate the identified mutations. Results: Among the 11 pairs of tissues specimens, 299 single nucleotide variants (SNVs) in 75 genes were identified. The most common pattern of base pair substitutions was T:A>C:G (49.83%), followed by C:G>T:A (18.06%) and C:G>G:C (15.05%). The altered genes were mainly implicated in MAPK (mitogen-activated protein kinase), PPAR (peroxisome proliferator-activated receptors), and p53 signaling pathways. In addition, 12 novel identified driver genes were validated by Sanger sequencing. The mutations of FAM133A, DPCR1, JAK1, C10orf10, EPB41L3, GPRASP1 and IWS1 exhibited in multiple PTC cases. Furthermore, the PTC cases exhibited individual mutational signature, even the same gene might present different mutational status in different cases. Conclusion: Multiple PTC-related somatic mutations and signal pathways are identified via WES and Sanger sequencing methods. The novel identified mutations in genes such as FAM133A, DPCR1, and JAK1 may be potential therapeutic targets for PTC patients.

Abstract 2426: Detection of somatic mutations associated with pulmonary metastasis of osteosarcoma by whole exome sequencing

2016 ◽  
Author(s):  
Shintaro Iwata ◽  
Yasutoshi Tatsumi ◽  
Tsukasa Yonemoto ◽  
Hiroto Kamoda ◽  
Takeshi Ishii ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pulmonary Metastasis ◽  
Somatic Mutations ◽  
Whole Exome

scholarly journals USP8 and TP53 Drivers are Associated with CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors

2020 ◽  
Author(s):  
Andrew V Uzilov ◽  
Patricia Taik ◽  
Khadeen C Cheesman ◽  
Pedram Javanmard ◽  
Kai Ying ◽  
...  
Keyword(s):  
At Risk ◽  
Aggressive Behavior ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutations ◽  
Care Center ◽  
Tertiary Care ◽  
Driver Genes ◽  
Cushing Disease ◽  
Whole Exome

Abstract Context Pituitary corticotroph adenomas are rare tumors that can be associated with excess adrenocorticotropin (ACTH) and adrenal cortisol production, resulting in the clinically debilitating endocrine condition Cushing disease. A subset of corticotroph tumors behave aggressively, and genomic drivers behind the development of these tumors are largely unknown. Objective To investigate genomic drivers of corticotroph tumors at risk for aggressive behavior. Design Whole-exome sequencing of patient-matched corticotroph tumor and normal deoxyribonucleic acid (DNA) from a patient cohort enriched for tumors at risk for aggressive behavior. Setting Tertiary care center Patients Twenty-seven corticotroph tumors from 22 patients were analyzed. Twelve tumors were macroadenomas, of which 6 were silent ACTH tumors, 2 were Crooke’s cell tumors, and 1 was a corticotroph carcinoma. Intervention Whole-exome sequencing. Main outcome measure Somatic mutation genomic biomarkers. Results We found recurrent somatic mutations in USP8 and TP53 genes, both with higher allelic fractions than other somatic mutations. These mutations were mutually exclusive, with TP53 mutations occurring only in USP8 wildtype (WT) tumors, indicating they may be independent driver genes. USP8-WT tumors were characterized by extensive somatic copy number variation compared with USP8-mutated tumors. Independent of molecular driver status, we found an association between invasiveness, macroadenomas, and aneuploidy. Conclusions Our data suggest that corticotroph tumors may be categorized into a USP8-mutated, genome-stable subtype versus a USP8-WT, genome-disrupted subtype, the latter of which has a TP53-mutated subtype with high level of chromosome instability. These findings could help identify high risk corticotroph tumors, namely those with widespread CNV, that may need closer monitoring and more aggressive treatment.

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