Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

Ruhen, Olivia; Mirzai, Bob; Clark, Michael E.; Nguyen, Bella; Salomón, Carlos; Erber, Wendy N.; Meehan, Katie

doi:10.3390/biomedicines9010014

Cited by 16 publications

(14 citation statements)

References 28 publications

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“…This method has been utilized by some previous studies to clinically identify the cytogenetics [16,17]. In the meantime, circulating Cell-free DNA evaluation by this method has also been reported and thought to be valuable in predicting the prognosis or chemotherapy resistance in non-small cell lung cancer and breast cancer [18][19][20]. Based on these reports, LPWGS is thought to be a reliable method in determine large segments alterations of cancer genomes.…”

Section: Discussionmentioning

confidence: 99%

High chromosome instability identified by low-pass whole-genome sequencing assay is associated with TP53 copy loss and worse prognosis in BRCA1 germline mutation breast cancer

et al. 2021

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Background Though BRCA1 mutation is the most susceptible factor of breast cancer, its prognostic value is disputable. Here in this study, we use a novel method which based on whole-genome analysis to evaluate the chromosome instability (CIN) value and identified the potential relationship between CIN and prognosis of breast cancer patients with germline-BRCA1 mutation. Materials and methods Sanger sequencing or a 98-gene panel sequencing assay was used to screen for BRCA1 germline small mutations in 1151 breast cancer patients with high-risk factors. MLPA assay was employed to screen BRCA1 large genomic rearrangements in familial breast cancer patients with BRCA1 negative for small mutations. Thirty-two samples with unique BRCA1 germline mutation patterns were further subjected to CIN evaluation by LPWGS (low-pass whole-genome sequencing) technology. Results Firstly, 113 patients with germline BRCA1 mutations were screened from the cohort. Further CIN analysis by the LPWGS assay indicated that CIN was independent from the mutation location or type of BRCA1. Patients with high CIN status had shorter disease-free survival rates (DFS) (HR = 6.54, 95% CI 1.30–32.98, P = 0.034). The TP53 copy loss was also characterized by LPWGS assay. The rates of TP53 copy loss in CIN high and CIN low groups were 85.71% (12/14) and 16.67% (3/18), respectively. Conclusion CIN-high is a prognostic factor correlated with shorter DFS and was independent with the germline BRCA1 mutation pattern. Higher CIN values were significantly correlated with TP53 copy loss in breast cancer patients with germline BRCA1 mutation. Our results revealed a reliable molecular parameter for distinguishing patients with poor prognosis from the BRCA1-mutated breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

High chromosome instability identified by low-pass whole-genome sequencing assay is associated with TP53 copy loss and worse prognosis in BRCA1 germline mutation breast cancer

et al. 2021

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“…This difference could be due to the difference in DNA degradation during storage in FFPE tissue blocks [138,139]. In another study, only one case presented a lower sensitivity to tumor driver CNVs of breast cancer with EV DNA compared with ctDNA [133].…”

Section: Wgs and Wesmentioning

confidence: 95%

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Hur

Lee

2021

Cancers

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Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors. The existence of DNA and its stability make EVs a useful source of biomarkers. However, fundamental research on EV DNA remains limited, and many aspects of EV DNA are poorly understood. This review examines the known characteristics of EV DNA, biogenesis of DNA-containing EVs, methylation, and next-generation sequencing (NGS) analysis using EV DNA for biomarker detection. On the basis of this knowledge, this review explores how EV DNA can be incorporated into diagnosis and prognosis in clinical settings, as well as gene transfer of EV DNA and its therapeutic potential.

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“…This technology demonstrated matrix metalloproteases-14 on extracellular vesicles to detect cell invasiveness in vitro ( Zhang et al, 2020 ). However, an investigation into the comparison between extracellular DNA and circulating tumor DNA found that while copy number variants were both detectable in two kinds of DNA, circulating tumor DNA have better sensitivity in serial monitor of BC ( Ruhen et al, 2020 ).…”

Section: Therapeutic Applications Of Exosomes In Breast Cancermentioning

confidence: 99%

The Advancing Roles of Exosomes in Breast Cancer

Wang

Sun

Huang

et al. 2021

Front. Cell Dev. Biol.

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Breast cancer (BC) develops from breast tissue and is the most common aggressive malignant tumor in women worldwide. Although advanced treatment strategies have been applied and reduced current mortality rates, BC control remains unsatisfactory. It is essential to elucidate the underlying molecular mechanisms to assist clinical options. Exosomes are a type of extracellular vesicles and mediate cellular communications by delivering various biomolecules (oncogenes, oncomiRs, proteins, and even pharmacological compounds). These bioactive molecules can be transferred to change the transcriptome of target cells and influence tumor-related signaling pathways. Extensive studies have implicated exosomes in BC biology, including therapeutic resistance and the surrounding microenvironment. This review focuses on discussing the functions of exosomes in tumor treatment resistance, invasion and metastasis of BC. Moreover, we will also summarize multiple interactions between exosomes and the BC tumor microenvironment. Finally, we propose promising clinical applications of exosomes in BC.

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Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient

Cited by 16 publications

References 28 publications

High chromosome instability identified by low-pass whole-genome sequencing assay is associated with TP53 copy loss and worse prognosis in BRCA1 germline mutation breast cancer

High chromosome instability identified by low-pass whole-genome sequencing assay is associated with TP53 copy loss and worse prognosis in BRCA1 germline mutation breast cancer

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

The Advancing Roles of Exosomes in Breast Cancer

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