The extent of whole-genome copy number alterations predicts aggressive features in primary melanomas

2016 ◽  
Vol 29 (2) ◽  
pp. 163-175 ◽  
Author(s):  
Greta Gandolfi ◽  
Caterina Longo ◽  
Elvira Moscarella ◽  
Iris Zalaudek ◽  
Valentina Sancisi ◽  
...  
Keyword(s):  
Copy Number ◽  
Whole Genome ◽  
Copy Number Alterations ◽  
Genome Copy ◽  
Genome Copy Number

The use of whole genome copy number variation (CNV) to measure genomic instability in mCRPC CTCs.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 307-307
Author(s):  
Yipeng Wang ◽  
Stephanie Greene ◽  
Angel Rodriguez ◽  
Jerry Lee ◽  
Mark Landers ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genomic Instability ◽  
Copy Number ◽  
Parp Inhibitors ◽  
Whole Genome ◽  
Copy Number Alterations ◽  
Genome Copy ◽  
Pten Loss ◽  
Dna Repair Gene ◽  
Genome Copy Number

307 Background: AR targeted therapies in combination with PARP inhibitors have recently shown efficacy in mCRPC patients with specific DNA repair gene mutations in metastatic tissue biopsies. Homologous recombination DNA repair deficiencies (HRD), associated with response to PARP inhibitors, can also be assessed by genomic instability/scarring. Accurate genomic scarring measurement in tumors can be confounded by intra-tumor heterogeneity and/or non-tumor genome contamination. To better identify PARPi sensitivity in mCRPC patients, we developed a genomic instability and scarring assay starting from single CTCs. Methods: VCaP, LnCaP or PC3 cell lines were spiked into healthy donor blood. Individual spiked cells were identified and recovered for genomic analysis using the standard Epic CTC assay. Post recovery, cells were lysed, whole genome amplified, constructed into shotgun libraries and sequenced to ~2M 2x150bp PE reads. Following alignment, whole genome copy number and instability analysis was performed to identify large scale transitions (LST, n of chromosomal breaks between adjacent regions of at least 10 Mb), % of genome altered (percentage of 1Mbp bins with copy number alterations), as well as specific tumor suppressor/oncogene copy number alterations. The association of PTEN loss with increases in genomic instability and scaring was performed. Results: Loss of PTEN function was previously shown to be associated with genomic instability. Our assessment of PTEN deletion was confirmed in PC3, while at least one genomic copy was observed in LnCaP and VCaP. The number of LSTs and % of genome altered was higher in PC3 (n = 19 +/- 3; 9.3% +/- 2.6%) than both VCaP and LnCap (n = 8 +/- 2; 6.1% +/- 0.4%). Conclusions: The association of higher genomic instability in a PTEN null cell line (PC3) vs. those with either heterozygous (LnCaP) or wild type (VCaP) PTEN status, matches published reports associating PTEN loss with increased genomic instability. Although, PC3 only demonstrates mild PARPi sensitivity in vitro, the detection of increased genomic scarring vs. cells with at least 1 functional PTEN allele confirms the assays ability to quantify genome instability at the single cell level from CTCs in a liquid biopsy.

scholarly journals Nuclear-cytoplasmic balance: whole genome duplications induce elevated organellar genome copy number

2021 ◽  
Author(s):  
Matheus Fernandes Gyorfy ◽  
Emma R Miller ◽  
Justin L Conover ◽  
Corrinne E Grover ◽  
Jonathan F Wendel ◽  
...  
Keyword(s):  
Copy Number ◽  
Nuclear Genome ◽  
Plant Genome ◽  
Whole Genome ◽  
Genome Copy ◽  
Relative Copy Number ◽  
Organellar Genome ◽  
Plastid Genomes ◽  
Copy Numbers ◽  
Genome Copy Number

The plant genome is partitioned across three distinct subcellular compartments: the nucleus, mitochondria, and plastids. Successful coordination of gene expression among these organellar genomes and the nuclear genome is critical for plant function and fitness. Whole genome duplication events (WGDs) in the nucleus have played a major role in the diversification of land plants and are expected to perturb the relative copy number (stoichiometry) of nuclear, mitochondrial, and plastid genomes. Thus, elucidating the mechanisms whereby plant cells respond to the cytonuclear stoichiometric imbalance that follow WGDs represents an important yet underexplored question in understanding the evolutionary consequences of genome doubling. We used droplet digital PCR (ddPCR) to investigate the relationship between nuclear and organellar genome copy numbers in allopolyploids and their diploid progenitors in both wheat and Arabidopsis. Polyploids exhibit elevated organellar genome copy numbers per cell, largely preserving the cytonuclear stoichiometry observed in diploids despite the change in nuclear genome copy number. To investigate the timescale over which cytonuclear stoichiometry may respond to WGD, we also estimated organellar genome copy number in Arabidopsis synthetic autopolyploids and in a haploid-induced diploid line. We observed corresponding changes in organellar genome copy number in these laboratory-generated lines, indicating that at least some of the cellular response to cytonuclear stoichiometric imbalance is immediate following WGD. We conclude that increases in organellar genome copy numbers represent a common response to polyploidization, suggesting that maintenance of cytonuclear stoichiometry is an important component in establishing polyploid lineages.

Integrative whole-genome copy number analysis and mutation profiling of FFPE brain tumor specimens and potential in designing multi-arm clinical trials.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 11098-11098
Author(s):  
Shakti Ramkissoon ◽  
Wenya L. Bi ◽  
Sam Haidar ◽  
Jane B. Cryan ◽  
David A. Reardon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Tumor ◽  
Copy Number ◽  
Whole Genome ◽  
Copy Number Analysis ◽  
Genome Copy ◽  
Genome Copy Number ◽  
Mutation Profiling

scholarly journals Whole-genome copy number variation analysis in anophthalmia and microphthalmia

2013 ◽  
Vol 84 (5) ◽  
pp. 473-481 ◽  
Author(s):  
KF Schilter ◽  
LM Reis ◽  
A Schneider ◽  
TM Bardakjian ◽  
O Abdul-Rahman ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Whole Genome ◽  
Variation Analysis ◽  
Genome Copy ◽  
Copy Number Variation Analysis ◽  
Number Variation ◽  
Genome Copy Number

scholarly journals Sparse representation and Bayesian detection of genome copy number alterations from microarray data

2008 ◽  
Vol 24 (3) ◽  
pp. 309-318 ◽  
Author(s):  
Roger Pique-Regi ◽  
Jordi Monso-Varona ◽  
Antonio Ortega ◽  
Robert C. Seeger ◽  
Timothy J. Triche ◽  
...  
Keyword(s):  
Sparse Representation ◽  
Microarray Data ◽  
Copy Number ◽  
Copy Number Alterations ◽  
Genome Copy ◽  
Genome Copy Number
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