Circulating tumour DNA analysis demonstrates spatial mutational heterogeneity that coincides with disease relapse in myeloma

Leukemia ◽  
2016 ◽  
Vol 31 (8) ◽  
pp. 1695-1705 ◽  
Author(s):  
S Mithraprabhu ◽  
T Khong ◽  
M Ramachandran ◽  
A Chow ◽  
D Klarica ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Disease Relapse ◽  
Circulating Tumour Dna

scholarly journals Development of circulating tumour DNA analysis for gastrointestinal cancers

ESMO Open ◽  
2020 ◽  
Vol 5 (Suppl 1) ◽  
pp. e000600 ◽  
Author(s):  
Yoshiaki Nakamura ◽  
Kohei Shitara
Keyword(s):  
Dna Analysis ◽  
Residual Disease ◽  
Turnaround Time ◽  
Resistance Mechanisms ◽  
Detection Methods ◽  
Comprehensive Genomic Profiling ◽  
Gi Cancers ◽  
Ctdna Analysis ◽  
Next Generation Sequencing Ngs ◽  
Circulating Tumour Dna

Comprehensive genomic profiling using next-generation sequencing (NGS) enables the identification of multiple genomic biomarkers established in advanced gastrointestinal (GI) cancers. However, tissue-based NGS has limitations, such as long turnaround time and failure to detect tumour heterogeneity. Recently, the analysis of circulating tumour DNA (ctDNA) using polymerase chain reaction-based or NGS-based methods has demonstrated the capability to detect genomic alterations with high accuracy compared with tumour tissue analysis with short turnaround time and identify heterogeneous resistance mechanisms. Furthermore, ctDNA analysis can be repeatedly performed on disease progression to clarify resistant clones. Clinical trials that test the outcome of a selected targeted therapy based on a ctDNA result are ongoing to prospectively evaluate the clinical utility of ctDNA analysis. Furthermore, the improvement of ctDNA analysis beyond current technical limits of mutation-based ctDNA detection methods has expanded the potential for detecting the presence of tumours in patients with no clinically evident disease, such as minimal residual disease and early cancer. Although a careful understanding of the advantages and limitations are required and further prospective studies are needed, the ctDNA analysis has the potential to overcome several challenges in the treatment of various types of cancers at all stages, including GI cancers.

scholarly journals Circulating tumour DNA analysis in multiple myeloma

Oncotarget ◽  
2017 ◽  
Vol 8 (53) ◽  
pp. 90610-90611 ◽  
Author(s):  
Sridurga Mithraprabhu ◽  
Andrew Spencer
Keyword(s):  
Multiple Myeloma ◽  
Dna Analysis ◽  
Circulating Tumour Dna

scholarly journals Circulating tumour DNA analysis predicts relapse following resection in stage II and III melanoma

2018 ◽  
Vol 29 ◽  
pp. viii14-viii15
Author(s):  
L. Tan ◽  
S.K. Sandhu ◽  
R. Lee ◽  
J. Li ◽  
J. Callahan ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Stage Ii ◽  
Circulating Tumour Dna

scholarly journals Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial

2020 ◽  
Vol 21 (10) ◽  
pp. 1296-1308 ◽  
Author(s):  
Nicholas C Turner ◽  
Belinda Kingston ◽  
Lucy S Kilburn ◽  
Sarah Kernaghan ◽  
Andrew M Wardley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Dna Analysis ◽  
Advanced Breast ◽  
Circulating Tumour Dna

scholarly journals Genomic profile of advanced breast cancer in circulating tumour DNA

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Belinda Kingston ◽  
Rosalind J. Cutts ◽  
Hannah Bye ◽  
Matthew Beaney ◽  
Giselle Walsh-Crestani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Dna Analysis ◽  
Advanced Breast ◽  
Genomic Profile ◽  
Resistance Mutations ◽  
Poor Overall Survival ◽  
Er Positive ◽  
Circulating Tumour Dna ◽  
Positive Breast Cancer

AbstractThe genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2− disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036). The fraction of cancer with a mutation, the clonal dominance of a mutation, varied between genes, and within hotspot mutations of ESR1 and PIK3CA. In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities.

Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14545-e14545
Author(s):  
Michele Ghidini ◽  
Jens Claus Hahne ◽  
Chiara Senti ◽  
Andrea Lampis ◽  
Margherita Ratti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dna Analysis ◽  
Copy Number Variations ◽  
Gene Variants ◽  
Disease Relapse ◽  
Resectable Disease ◽  
Circulating Free Dna ◽  
Post Surgery ◽  
Free Dna

e14545 Background: Liquid biopsies (LB) allow monitoring of genetically different and co-occurring cancer cell clones present in primary tumor and all metastatic sites in parallel. In metastatic colorectal cancer (mCRC), circulating-free DNA (cfDNA) can be relevant for monitoring treatment and identification of molecular alterations resulting in disease relapse often earlier than radiological examinations. Methods: Patients with mCRC at diagnosis and treated with chemotherapy (CT) in combination with antibodies (bevacizumab, cetuximab or panitumumab) before undergoing surgery for resectable disease were included in this study. LB were collected before therapy start, every four weeks during treatment, within ten days of radiological disease evaluation, at radiological relapse and until two months after relapse. Next generation sequencing based on plasma samples was performed (testing for mutations and copy number variations covering 77 genes). Results: From February 2016 to October 2018, 14 patients having surgery after first line treatment were included herein; median follow-up was 21.5 months. Five of them had RAS wild-type disease and received CT plus anti-EGFR treatment, while nine RAS mutated mCRC patients received bevacizumab. Surgery was radical in 10 cases, with no further treatment. In four cases, surgery was not radical and required further treatment. Disease relapse happened in seven cases, with subsequent death in three cases. In six out of seven cases, gene alterations were already detected in the pre-operative cfDNA. In the seven cases without disease relapse, gene variants were detected even after the surgery in two patients despite receiving radical resection. Median number of gene variants was two. Beside the well-established mutations in TP53 gene, both APC and ROS1 gene mutations were frequent, while further evaluations are required for the other variants detected. Conclusions: Evaluation of cfDNA mutations in LB from mCRC may be a useful tool for monitoring clinical response and predict treatment outcome. Moreover, this molecular analysis can help to subgroup patients with regard to risk of relapse after radical surgery. Indeed, cfDNA mutations present before surgery seem to be an indication for a higher risk of post-surgery disease relapse.

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