scholarly journals The feasibility of using liquid biopsies as a complementary assay for copy number aberration profiling in routinely collected paediatric cancer patient samples

2021 ◽  
Author(s):  
Ruben Van Paemel ◽  
Charlotte Vandeputte ◽  
Lennart Raman ◽  
Jolien Van Thorre ◽  
Leen Willems ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Copy Number ◽  
Copy Number Aberration ◽  
Paediatric Cancer ◽  
Liquid Biopsies ◽  
Paediatric Cancer Patient

scholarly journals LiquidCNA: tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations

2021 ◽  
Author(s):  
Eszter Lakatos ◽  
Helen Hockings ◽  
Maximilian Mossner ◽  
Michelle Lockley ◽  
Trevor A. Graham
Keyword(s):  
Copy Number ◽  
Evolutionary Dynamics ◽  
Cost Effective ◽  
Copy Number Alterations ◽  
Liquid Biopsies ◽  
Metastatic Lung ◽  
Low Pass ◽  
Somatic Copy Number Alterations

AbstractCell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally-invasive monitoring of tumour evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples based on somatic copy number alterations (SCNAs). LiquidCNA utilises SCNA profiles derived through cost-effective low-pass whole genome sequencing to automatically and simultaneously genotype and quantify the size of the dominant subclone without requiring prior knowledge of the genetic identity of the emerging clone. We demonstrate the accuracy of liquidCNA in synthetically generated sample sets and in vitro and in silico mixtures of cancer cell lines. Application in vivo in patients with metastatic lung cancer reveals the progressive emergence of a novel tumour sub-population. LiquidCNA is straightforward to use, computationally inexpensive and enables continuous monitoring of subclonal evolution to understand and control therapy-induced resistance.

scholarly journals Gamma Knife Radiosurgery does not alter the copy number aberration profile in sporadic vestibular schwannoma

2020 ◽  
Vol 149 (3) ◽  
pp. 373-381
Author(s):  
Aril Løge Håvik ◽  
Ove Bruland ◽  
Dhanushan Dhayalan ◽  
Morten Lund-Johansen ◽  
Per-Morten Knappskog
Keyword(s):  
Radiation Exposure ◽  
Gamma Knife ◽  
Vestibular Schwannoma ◽  
Copy Number ◽  
Statistical Tests ◽  
Gamma Knife Radiosurgery ◽  
Copy Number Aberration ◽  
Recurrent Event ◽  
Chromosome 22 ◽  
Increased Risk

Abstract Introduction Ionizing radiation is a known etiologic factor in tumorigenesis and its role in inducing malignancy in the treatment of vestibular schwannoma has been debated. The purpose of this study was to identify a copy number aberration (CNA) profile or specific CNAs associated with radiation exposure which could either implicate an increased risk of malignancy or elucidate a mechanism of treatment resistance. Methods 55 sporadic VS, including 18 treated with Gamma Knife Radiosurgery (GKRS), were subjected to DNA whole-genome microarray and/or whole-exome sequencing. CNAs were called and statistical tests were performed to identify any association with radiation exposure. Hierarchical clustering was used to identify CNA profiles associated with radiation exposure. Results A median of 7 (0–58) CNAs were identified across the 55 VS. Chromosome 22 aberration was the only recurrent event. A median aberrant cell fraction of 0.59 (0.25–0.94) was observed, indicating several genetic clones in VS. No CNA or CNA profile was associated with GKRS. Conclusion GKRS is not associated with an increase in CNAs or alteration of the CNA profile in VS, lending support to its low risk. This also implies that there is no major issue with GKRS treatment failure being due to CNAs. In agreement with previous studies, chromosome 22 aberration is the only recurrent CNA. VS consist of several genetic clones, addressing the need for further studies on the composition of cells in this tumor.

scholarly journals Assessing the performance of methods for copy number aberration detection from single-cell DNA sequencing data

2020 ◽  
Vol 16 (7) ◽  
pp. e1008012 ◽  
Author(s):  
Xian F. Mallory ◽  
Mohammadamin Edrisi ◽  
Nicholas Navin ◽  
Luay Nakhleh
Keyword(s):  
Dna Sequencing ◽  
Single Cell ◽  
Copy Number ◽  
Copy Number Aberration ◽  
Sequencing Data ◽  
Aberration Detection

scholarly journals Cancer Patient-Reported Preferences and Knowledge for Liquid Biopsies and Blood Biomarkers at a Comprehensive Cancer Center

2020 ◽  
Vol Volume 12 ◽  
pp. 1163-1173
Author(s):  
Min Joon Lee ◽  
Katrina Hueniken ◽  
Nathan Kuehne ◽  
Lin Lu ◽  
Shirley Xue Jiang ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Blood Biomarkers ◽  
Liquid Biopsies ◽  
Patient Reported

scholarly journals Impressive response to immunotherapy in a metastatic gastric cancer patient: could somatic copy number alterations help patient selection?

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Gustavo dos Santos Fernandes ◽  
Daniel da Motta Girardi ◽  
Luiza Dib Batista Bugiato Faria ◽  
João Paulo Giacomini Bernardes ◽  
Renata de Almeida Coudry
Keyword(s):  
Gastric Cancer ◽  
Cancer Patient ◽  
Patient Selection ◽  
Gastric Cancer Patient ◽  
Copy Number ◽  
Metastatic Gastric Cancer ◽  
Copy Number Alterations ◽  
Somatic Copy Number Alterations

PIK3CA copy number aberration and activation of the PI3K-AKT-mTOR pathway in evolving disease states of penile cancer

2017 ◽  
Vol 16 (3) ◽  
pp. e1228-e1229
Author(s):  
A. Adimonye ◽  
E. Stankiewicz ◽  
S. Nicholson ◽  
E. Hall ◽  
S. Kudahetti ◽  
...  
Keyword(s):  
Copy Number ◽  
Penile Cancer ◽  
Copy Number Aberration ◽  
Mtor Pathway ◽  
Disease States

Prevalence and heterogeneity of androgen receptor splice variants and intra-AR structural variation in patient with castration-resistant prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11530-11530
Author(s):  
Luc Yves Dirix ◽  
Bram De Laere ◽  
Pieter-Jan van Dam ◽  
Tom Whitington ◽  
Markus Mayrhofer ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Splice Variant ◽  
Copy Number ◽  
Structural Variation ◽  
Splice Variants ◽  
Endocrine Resistance ◽  
Endocrine Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Liquid Biopsies ◽  
Multicentric Study

11530 Background: Androgen receptor splice variant 7 (AR-V7) is linked to a priori resistance to abiraterone acetate and enzalutamide. However, AR-V7 negativity does not necessarily indicate responsiveness and up to 20% of AR-V7 positive patients do demonstrate moderate response to these second-line endocrine therapies. Methods: Peripheral blood samples from patients with CRPC (n = 30) starting a new line of systemic therapy were subjected to comprehensive profiling of AR. AR splice variant (ARV) profiling for eight isoforms was performed by targeted RNA-Seq on CellSearch-enriched circulating tumour cells. Low-pass whole-genome and targeted sequencing of the entire AR gene in plasma-derived circulating cell-free DNA allowed the assessment of copy number status and structural rearrangements, respectively. ARV expression, structural variation, copy number alterations and ligand-binding domain mutations were combined and correlated to clinicopathologic parameters. Results: Twenty-five out of 30 patients (83%) demonstrated an aberration in AR. Twenty out of 30 patients (66.7%) demonstrated AR amplifications. Interestingly, 15/30 patients had intra-AR structural variants, of whom 14 expressed ARVs. In the context of endocrine treatment, 15/26 (57.7%) patients were ARV-positive with 13/15 patients having less than 6 months benefit from their therapy (Fisher’s exact test, p = 0.0115). ARV expression was heterogeneous with 10/15 ARV-positive patients expressing several ARV. Notably, AR-V7 was most frequently detected, however AR-V3 was 3.5x more abundant (Wilcox signed rank, p = 0.0029). In 17 patients, a baseline AR profile was available and demonstrated how having any ARV was associated with progression-free survival (HR: 4.53, 95%CI: 1.424–14.41; p = 0.0105). In the poor response group, 6/17 (35.2%) were AR-V7 negative, of whom 4 carried other AR aberrations. Conclusions: Comprehensive AR profiling on liquid biopsies is feasible and provides new insights into the mechanisms driving endocrine resistance. Clinical validation, by means of a non-interventional, prospective and multicentric study, is essential and currently ongoing.

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