scholarly journals Reliability of Whole-Exome Sequencing for Assessing Intratumor Genetic Heterogeneity

Cell Reports ◽  
2018 ◽  
Vol 25 (6) ◽  
pp. 1446-1457 ◽  
Author(s):  
Weiwei Shi ◽  
Charlotte K.Y. Ng ◽  
Raymond S. Lim ◽  
Tingting Jiang ◽  
Sushant Kumar ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing to Decipher the Genetic Heterogeneity of Hearing Loss in a Chinese Family with Deaf by Deaf Mating

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109178 ◽  
Author(s):  
Jie Qing ◽  
Denise Yan ◽  
Yuan Zhou ◽  
Qiong Liu ◽  
Weijing Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Chinese Family ◽  
Whole Exome

scholarly journals Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy

2015 ◽  
Vol 20 (2) ◽  
pp. 176-182 ◽  
Author(s):  
G McMichael ◽  
M N Bainbridge ◽  
E Haan ◽  
M Corbett ◽  
A Gardner ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Whole Exome

Whole-exome sequencing in osteosarcoma with distinct prognosis reveals disparate genetic heterogeneity

2021 ◽  
Author(s):  
Weifeng Liu ◽  
Renxian Wang ◽  
Yanrui Zhang ◽  
Huina Wang ◽  
Zhen Huang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Whole Exome

scholarly journals Reliability of Whole-Exome Sequencing for Assessing Intratumor Genetic Heterogeneity

2018 ◽  
Author(s):  
Weiwei Shi ◽  
Charlotte K. Y. Ng ◽  
Raymond S. Lim ◽  
Tingting Jiang ◽  
Sushant Kumar ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
False Positive ◽  
Amplicon Sequencing ◽  
Technical Noise ◽  
Whole Exome ◽  
High Depth

SUMMARYMulti-region sequencing is used to detect intratumor genetic heterogeneity (ITGH) in tumors. To assess whether genuine ITGH can be distinguished from sequencing artifacts, we whole-exome sequenced (WES) three anatomically distinct regions of the same tumor with technical replicates to estimate technical noise. Somatic variants were detected with three different WES pipelines and subsequently validated by high-depth amplicon sequencing. The cancer-only pipeline was unreliable, with about 69% of the identified somatic variants being false positive. Even with matched normal DNA where 82% of the somatic variants were detected reliably, only 36%-78% were found consistently in technical replicate pairs. Overall 34%-80% of the discordant somatic variants, which could be interpreted as ITGH, were found to constitute technical noise. Excluding mutations affecting low mappability regions or occurring in certain mutational contexts was found to reduce artifacts, yet detection of subclonal mutations by WES in the absence of orthogonal validation remains unreliable.

Whole-exome sequencing of single circulating tumor cells is a useful tool for studying the intrapatient genetic heterogeneity in metastatic prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 148-148 ◽  
Author(s):  
Vincent Faugeroux ◽  
Celine Lefebvre ◽  
Emma Pailler ◽  
Valerie Pierron ◽  
Fanny Billiot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
Exome Sequencing ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Castration Resistant Prostate Cancer ◽  
Illumina Hiseq ◽  
Whole Exome

148 Background: Molecular characterization of metastatic castration resistant prostate cancer (mCRPC) is limited by tumor tissue availability. The analysis of circulating tumor cells (CTC) offers an attractive noninvasive surrogate option to analyze molecular alterations. We report whole exome sequencing (WES) of CTCs at the single cell level in mCRPC patients. Methods: Blood samples were drawn from 11 enzalutamide or abiraterone pre-treated mCRPC patients enrolled in the clinical program MOSCATO (NCT02613962). CTC enrichment, immunofluorescent detection and single cell isolation were performed using three methods (ISET filtration, CellSearch and the VyCap puncher system and RosetteSep enrichment) to obtain pools of 1-10 CTCs with distinct epithelial or mesenchymal phenotypes. After Whole Genome Amplification (WGA), WES was performed on the Illumina HiSeq 2000 platform. GATK Haplotype Caller enabled identification of germline polymorphisms from each patient in normal DNA, metastatic sample and CTCs in order to consider WGA induced bias. The detection of sSNV in tumor biopsies and CTCs was assessed with Mutect and IndelGenotyper respectively. Results: 189 WGA of CTC pools were performed. 34 pools of phenotypically different CTCs from 7 patients were selected and sequenced. Mean coverage of 51% was obtained at a sequencing depth of 10X. Allelic drop out was lower for CTC pools containing 5-10 cells. 17/34 (50%) CTC samples had shared sSNV with the paired tumor sample (range 0.35%-68%) Epithelial CTCs had more shared sSNV with metastatic biopsies than CTCs of other phenotypes but shared sSNV were also detected in large non epithelial CTC pointing out a high level of genetic heterogeneity between CTC. Overall, 89 deleterious protein-coding mutations were found only in pools of CTC, including mutations affecting oncogenic drivers such as MAPK1, HSP90AB1 or KDM5B. Conclusions: We present single cell WES of CTCs harboring distinct phenotypes. The detection of shared sSNV between CTC pools and corresponding biopsy could validate the use of CTCs as a liquid biopsy. The finding of sSNV specific to CTCs could offer additional data on tumor heterogeneity.

scholarly journals Reliability of Whole-Exome Sequencing for Assessing Intratumor Genetic Heterogeneity

2018 ◽  
Author(s):  
Weiwei Shi ◽  
Charlotte K.Y. Ng ◽  
Raymond S. Lim ◽  
Tingting Jiang ◽  
Sushant Kumar ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Heterogeneity ◽  
Whole Exome
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