scholarly journals Shallow whole-genome sequencing: a useful, easy to apply molecular technique for CNA detection on FFPE tumor tissue—a glioma-driven study

2022 ◽  
Kim Van der Eecken ◽  
Malaïka Van der Linden ◽  
Lennart Raman ◽  
David Creytens ◽  
Franceska Dedeurwaerdere ◽  
2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi15-vi15
Stephen J Bagley ◽  
Jacob Till ◽  
Aseel Abdalla ◽  
MacLean Nasrallah ◽  
Tomer Lauterman ◽  

Abstract BACKGROUND Plasma circulating tumor DNA (ctDNA) is rarely detectable by traditional methods in patients with GBM. As a result, unlike in lung and other cancers, serial next generation sequencing of ctDNA for monitoring GBM tumor burden has been challenging. In light of the low tumor fraction (TF) of DNA fragments in GBM patient plasma and the urgent need to improve upon MRI for tracking GBM tumor burden, we conducted a pilot study in patients with newly diagnosed GBM using the C2 intelligence platform (C2i Genomics), which leverages genome-wide mutational integration for highly sensitive ctDNA detection. METHODS Plasma was collected pre- and post-operatively in patients with newly diagnosed GBM undergoing surgical resection/biopsy. cfDNA was extracted, quantified, and analyzed for fragment size. Genomic DNA (gDNA) was extracted from matched tumor tissue. Whole genome sequencing (WGS) was performed on both gDNA and cfDNA. A specific copy number alteration (CNA) compendium was created for each patient to generate a readout of TF (Zviran, Nat Medicine 2020). We assessed the association between TF at post-operative day 1 (a surrogate for residual disease) and OS, adjusting for other prognostic factors using Cox regression. RESULTS 37 patients were enrolled. For samples with high tumor fraction (n=5), a statistically significant (p< 1e-4) correlation between CNA profiles of tumor tissue and plasma samples was observed. Post-operative TF above the median value was associated with inferior OS (median 7.7 vs. 19.3 months, p=0.019). This association persisted after adjusting for age, O6-methylguanine-DNA methyltransferase methylation status, extent of resection, and performance status (adjusted HR 2.5, 95% CI 1.1-5.6, p=0.03). CONCLUSION Genome-wide mutational integration enables ultra-sensitive detection of ctDNA in GBM patient plasma. Post-operative TF measured by the C2i test is independently associated with OS in newly diagnosed GBM, providing the foundation to evaluate this technology for personalized prognostication and disease monitoring.

2020 ◽  
Yongping Li ◽  
Hao Yuan ◽  
Bin Zhang ◽  
Xiaofei Jiang ◽  
Minghua Yu ◽  

Abstract Backgroud: Tumor tissues are usually highly heterogeneous and difficult to characterize which could mislead treatment strategy. Circulating tumor cells (CTCs) represent the most active and invasive tumor cells. This study retrospectively investigated the feasibility of individualized treatment of breast cancer patients based on genome sequencing of single cell CTC. Twenty-four CTCs were identified in three patients with breast cancer. For each patient, one polyploid CTC was captured and on which the whole genome sequencing (WGS) was performed. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies, and monitored disease progression. Results: Patient ID1 and ID2 are with Her-2 protein overexpression in primary tumors and HER2 gene amplification in the DNA of CTCs. In patient ID3, histological examination of primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed that the HER2 gene was amplified. After adjusting treatment by adding Her-2 inhibitors according to the results of CTC sequencing, the liver metastases and pleural effusion were significantly reduced 2 month later, CTC number and ctDNA burden were decreased, and 18-month progression-free survival (PFS) was recorded. In addition, some potential therapeutic targets and mutations in drug-resistant genes were found. Conclusions: The results of CTC sequencing effectively guided treatment of a patient with HER2 gene amplification in CTC but with Her-2 negative on tumor tissue. CTC sequencing is useful in resolving the heterogeneity of tumors and providing precision medicine for patients.

2018 ◽  
Mark Stevenson ◽  
Alistair T Pagnamenta ◽  
Heather G Mack ◽  
Judith A Savige ◽  
Kate E Lines ◽  

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 146-146
D. M. Bickhart ◽  
L. Xu ◽  
J. L. Hutchison ◽  
J. B. Cole ◽  
D. J. Null ◽  

Ainhoa Arrieta-Gisasola ◽  
Aitor Atxaerandio Landa ◽  
Javier Garaizar ◽  
Joseba Bikandi ◽  
José Karkamo ◽  

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