Whole-genome sequencing of circulating tumor DNA reveals relevance of focal amplifications for the management of metastatic prostate cancer

2016 ◽  
Vol 61 ◽  
pp. S12
Author(s):  
J. Belic ◽  
P. Ulz ◽  
R. Graf ◽  
M. Auer ◽  
K. Fischereder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Metastatic Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Whole Genome ◽  
Tumor Dna

scholarly journals Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer

2019 ◽  
pp. 1-13 ◽  
Author(s):  
S. Thomas Hennigan ◽  
Shana Y. Trostel ◽  
Nicholas T. Terrigino ◽  
Olga S. Voznesensky ◽  
Rachel J. Schaefer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Metastatic Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Localized Prostate Cancer ◽  
Whole Genome ◽  
Aggressive Disease ◽  
Low Pass ◽  
Tumor Dna

PURPOSE Despite decreased screening-based detection of clinically insignificant tumors, most diagnosed prostate cancers are still indolent, indicating a need for better strategies for detection of clinically significant disease before treatment. We hypothesized that patients with detectable circulating tumor DNA (ctDNA) were more likely to harbor aggressive disease. METHODS We applied ultra-low-pass whole-genome sequencing to profile cell-free DNA from 112 patients diagnosed with localized prostate cancer and performed targeted resequencing of plasma DNA for somatic mutations previously identified in matched solid tumor in nine cases. We also performed similar analyses of data from patients with metastatic prostate cancer. RESULTS In all cases of localized prostate cancer, even in clinically high-risk patients who subsequently had recurrent disease, ultra-low-pass whole-genome sequencing and targeted resequencing did not detect ctDNA in plasma acquired before surgery or before recurrence. In contrast, using both approaches, ctDNA was detected in patients with metastatic prostate cancer. CONCLUSION Our findings demonstrate clear differences between localized and advanced prostate cancer with respect to the dissemination and detectability of ctDNA. Because allele-specific alterations in ctDNA are below the threshold for detection in localized prostate cancer, other approaches to identify cell-free nucleic acids of tumor origin may demonstrate better specificity for aggressive disease.

scholarly journals Case Report: Circulating Tumor DNA Fraction Analysis Using Ultra-Low-Pass Whole-Genome Sequencing Correlates Response to Chemoradiation and Recurrence in Stage IV Small-Cell Carcinoma of the Cervix - A Longitudinal Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ata Abbas ◽  
Morgan Gruner ◽  
Jennifer Karohl ◽  
Peter G. Rose ◽  
Amy Joehlin-Price ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Small Cell Carcinoma ◽  
Genome Sequencing ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Response To Therapy ◽  
Whole Genome ◽  
Low Pass ◽  
Tumor Dna

Neuroendocrine carcinoma of the cervix is a rare and aggressive form of cervical cancer that presents with frequent metastasis at diagnosis and high recurrence rates. Primary treatment is multimodal, which often includes chemotherapy with or without radiation therapy. There are no data available to guide treatment for recurrence, and second-line therapies are extrapolated from small-cell lung carcinoma data. Close monitoring of these patients for recurrence is paramount. Evaluation of circulating tumor DNA (ctDNA) in the peripheral blood is an attractive approach due to its non-invasive nature. Ultra-low-pass whole-genome sequencing (ULP-WGS) can assess tumor burden and response to therapy and predict recurrence; however, data are lacking regarding the role of ULP-WGS in small-cell carcinoma of the cervix. This study demonstrates a patient whose response to chemotherapy and cancer recurrence was accurately monitored by ctDNA analysis using ULP-WGS and confirmed with radiologic imaging findings.

Abstract 2739: Low-pass whole genome sequencing detects copy number variations in circulating tumor DNA

2017 ◽  
Author(s):  
Xiaoji Chen ◽  
Jill M. Spoerke ◽  
Kathryn Yoh ◽  
Walter C. Darbonne ◽  
Ling-Yuh Huw ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Circulating Tumor Dna ◽  
Copy Number Variations ◽  
Whole Genome ◽  
Low Pass ◽  
Tumor Dna

scholarly journals Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Peter Peneder ◽  
Adrian M. Stütz ◽  
Didier Surdez ◽  
Manuela Krumbholz ◽  
Sabine Semper ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Ewing Sarcoma ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Whole Genome ◽  
Cell Free Dna ◽  
Genetic Aberrations ◽  
Free Dna ◽  
Tumor Dna

AbstractSequencing of cell-free DNA in the blood of cancer patients (liquid biopsy) provides attractive opportunities for early diagnosis, assessment of treatment response, and minimally invasive disease monitoring. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we introduce an integrated genetic/epigenetic analysis method and demonstrate its utility on 241 deep whole-genome sequencing profiles of 95 patients with Ewing sarcoma and 31 patients with other pediatric sarcomas. Our method achieves sensitive detection and classification of circulating tumor DNA in peripheral blood independent of any genetic alterations. Moreover, we benchmark different metrics for cell-free DNA fragmentation analysis, and we introduce the LIQUORICE algorithm for detecting circulating tumor DNA based on cancer-specific chromatin signatures. Finally, we combine several fragmentation-based metrics into an integrated machine learning classifier for liquid biopsy analysis that exploits widespread epigenetic deregulation and is tailored to cancers with low mutation rates. Clinical associations highlight the potential value of cfDNA fragmentation patterns as prognostic biomarkers in Ewing sarcoma. In summary, our study provides a comprehensive analysis of circulating tumor DNA beyond recurrent genetic aberrations, and it renders the benefits of liquid biopsy more readily accessible for childhood cancers.

scholarly journals Matched Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES) of Tumor Tissue with Circulating Tumor DNA (ctDNA) Analysis: Complementary Modalities in Clinical Practice

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1399 ◽  
Author(s):  
Robin Imperial ◽  
Marjan Nazer ◽  
Zaheer Ahmed ◽  
Audrey E. Kam ◽  
Timothy J. Pluard ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Exome Sequencing ◽  
Genome Sequencing ◽  
Systemic Therapy ◽  
Tumor Heterogeneity ◽  
Circulating Tumor Dna ◽  
Whole Genome ◽  
Whole Exome ◽  
Ctdna Analysis ◽  
Tumor Dna

Tumor heterogeneity, especially intratumoral heterogeneity, is a primary reason for treatment failure. A single biopsy may not reflect the complete genomic architecture of the tumor needed to make therapeutic decisions. Circulating tumor DNA (ctDNA) is believed to overcome these limitations. We analyzed concordance between ctDNA and whole-exome sequencing/whole-genome sequencing (WES/WGS) of tumor samples from patients with breast (n = 12), gastrointestinal (n = 20), lung (n = 19), and other tumor types (n = 13). Correlation in the driver, hotspot, and actionable alterations was studied. Three cases in which more-in-depth genomic analysis was required have been presented. A total 58% (37/64) of patients had at least one concordant mutation. Patients who had received systemic therapy before tissue next-generation sequencing (NGS) and ctDNA analysis showed high concordance (78% (21/27) vs. 43% (12/28) p = 0.01, respectively). Obtaining both NGS and ctDNA increased actionable alterations from 28% (18/64) to 52% (33/64) in our patients. Twenty-one patients had mutually exclusive actionable alterations seen only in either tissue NGS or ctDNA samples. Somatic hotspot mutation analysis showed significant discordance between tissue NGS and ctDNA analysis, denoting significant tumor heterogeneity in these malignancies. Increased tissue tumor mutation burden (TMB) positively correlated with the number of ctDNA mutations in patients who had received systemic therapy, but not in treatment-naïve patients. Prior systemic therapy and TMB may affect concordance and should be taken into consideration in future studies. Incorporating driver, actionable, and hotspot analysis may help to further refine the correlation between these two platforms. Tissue NGS and ctDNA are complimentary, and if done in conjunction, may increase the detection rate of actionable alterations and potentially therapeutic targets.

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