scholarly journals Whole-genome sequencing of an advanced case of small-cell gallbladder neuroendocrine carcinoma

2016 ◽  
Author(s):  
Maolan Li ◽  
Fatao Liu ◽  
Yijian Zhang ◽  
Xiangsong Wu ◽  
Wenguang Wu ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Neuroendocrine Carcinoma ◽  
Sulfur Metabolism ◽  
Metastatic Cancer ◽  
Small Cell ◽  
Cancer Tissue ◽  
Whole Genome ◽  
Advanced Case

AbstractThe majority of gallbladder cancer cases are discovered at later stages, which frequently leads to poor prognoses. Small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC) is a relatively rare histological type of gallbladder cancer, and its survival rate is exceptionally low because of its greater malignant potential. In addition, the genomic landscape of GB-SCNEC is rarely considered in treatment decisions. We performed whole-genome sequencing on an advanced case of GB-SCNEC. By analyzing the whole-genome sequencing data of the primary cancer tissue (76.29X coverage), lymphatic metastatic cancer tissue (73.92X coverage) and matched non-cancerous tissue (35.73X coverage), we identified approximately 900 high-quality somatic single nucleotide variants (SNVs), 109 of which were shared by both the primary and metastatic tumor tissues. Somatic non-synonymous coding variations with damaging impact in HMCN1 and CDH10 were observed in both the primary and metastatic tissue specimens. A pathway analysis of the genes mapped to the SNVs revealed gene enrichment associated with axon guidance, ERBB signaling, sulfur metabolism and calcium signaling. Furthermore, we identified 20 chromosomal rearrangements that included 11 deletions, 4 tandem duplications and 5 inversions that mapped to known genes. Two gene fusions, NCAM2-SGCZ and BTG3-CCDC40 were also discovered and validated by Sanger sequencing. Additionally, we identified genome-wide copy number variations and microsatellite instability. In this study, we identified novel biological markers of GB-SCNEC that may serve as valuable prognostic factors or indicators of treatment response in patients with GB-SCNEC with lymphatic metastasis.

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.

scholarly journals Author Correction: Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bella Nguyen ◽  
Nicholas C. Wong ◽  
Tim Semple ◽  
Michael Clark ◽  
Stephen Q. Wong ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Metastatic Cancer ◽  
Extracellular Vesicle ◽  
Whole Genome ◽  
Low Coverage

scholarly journals Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bella Nguyen ◽  
Nicholas C. Wong ◽  
Tim Semple ◽  
Michael Clark ◽  
Stephen Q. Wong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Squamous Cell ◽  
Metastatic Cancer ◽  
Extracellular Vesicle ◽  
Whole Genome ◽  
Ffpe Samples ◽  
Low Coverage

AbstractLow-coverage whole-genome sequencing (LC-WGS) can provide insight into oncogenic molecular changes. Serum extracellular vesicles (EV) represent a novel liquid biopsy source of tumoral DNA. This study compared copy number alteration (CNA) profiles generated from LC-WGS of formalin-fixed paraffin-embedded (FFPE) tumoral DNA and EV-DNA obtained from cancer patients. Patients with squamous cell carcinoma of the base of tongue (n = 3) and cutaneous squamous cell carcinoma (n = 2) were included. LC-WGS (0.5-1X coverage) was performed on FFPE-DNA and serum EV-DNA. Similarity between CNA profiles was analysed using QDNAseq. FFPE samples had a mean CNA of 31 (range 17–50) over 1.9 × 109 (range 1.0–2.6 × 109) bp in length, and EV samples had a mean CNA value of 17 (range 7–19) over 7.6 × 108 (range 2.9–15 × 108) bp in length. A mean of 8 (range 0–21) CNA over 5.9 × 108 (range 1.6–14 × 108) bp in length was found to overlap between EV and FFPE-derived samples per patient. Although the mean correlation efficient between samples was r = 0.34 (range − .08 to 0.99), this was not statistically significant (p > 0.05). Regions of highest deletion and duplication in FFPE samples were not well reflected in the EV-DNA. Selected CNA regions in EV-associated DNA were reflective of the primary tumor, however appreciation of global CNA and areas of most significant change was lost. The utility of LC-WGS of EV-derived DNA is likely limited to molecular alterations of known interest.

Prevalence and tissue concordance of BRCA2 copy number loss evaluated by single-cell, shallow whole genome sequencing of circulating tumor cells (CTCs) in castration-resistant prostate cancer (CRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5531-5531
Author(s):  
Ethan Barnett ◽  
Joseph Schonhoft ◽  
Nikolaus D. Schultz ◽  
Jerry Lee ◽  
Samir Zaidi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Single Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Genome Sequencing ◽  
Copy Number ◽  
Cellular Heterogeneity ◽  
Cancer Tissue ◽  
Whole Genome

5531 Background: Genomic studies have shown that up to 25% of prostate cancer tissue specimens harbor alterations in DNA Damage Repair (DDR) genes, which may sensitize the tumor to poly ADP-ribose polymerase inhibitors (PARPi). Trials evaluating PARPi in patients with DDR deficiencies have shown varied response rates and differences regarding which genomic alterations predict for sensitivity to these agents, with the majority of objective responses seen in BRCA2-altered tumors. These results highlight the need to develop biomarker assays which can predict benefit from PARPi therapy. Tissue and cell-free DNA (cfDNA) have been the most utilized sources of tumor material for analysis in this setting, but success rates of obtaining sufficient tumor for analysis from bone are low and detecting tumor-derived copy number variants (CNVs) in cfDNA is challenging. Circulating tumor cells (CTCs) represent an alternate source of genetic information, for which assays are available to isolate and sequence individual cells in a manner that eliminates background noise from stroma and healthy cells, while capturing inter-cellular heterogeneity. Methods: Blood samples, collected from 138 progressing metastatic CRPC patients within 30 days of a pre-treatment biopsy intended for sequencing using MSK-IMPACT, were sent to EPIC Sciences for CTC analysis. Detected CTCs underwent single cell, low pass whole genome sequencing. Prevalence and concordance of BRCA2 copy-loss, regardless of whether single copy or homozygous, was compared in matched tissue and CTC samples. Results: BRCA2 copy-loss was identified in 21% (23/108) and 50% (58/115) of successfully sequenced tissue and CTC samples, respectively. In the 58 patients with CTC-detected BRCA2 loss, BRCA2 loss was detected in 36% (220/565) of the sequenced CTCs, representing a median of 46% (range 4-100%) of CTCs found in each individual sample. When both sequencing assays were successful, BRCA2 loss was detected in CTCs in 84% (16/19) of the tissue-positive cases, whereas tissue sequencing detected BRCA2 loss in 35% (16/46) of CTC-positive cases. Conclusions: Data from this study supports the notion that single-cell CTC sequencing can detect BRCA2 copy-loss at a high frequency, including cases that were negative in tissue, while also characterizing inter-cellular heterogeneity. Further studies will investigate whether CTC BRCA2 copy-loss can predict the likelihood of response to PARPi.

scholarly journals Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

2017 ◽  
Vol 77 (16) ◽  
pp. 4530-4541 ◽  
Author(s):  
Natali Gulbahce ◽  
Mark Jesus M. Magbanua ◽  
Robert Chin ◽  
Misha R. Agarwal ◽  
Xuhao Luo ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Whole Genome Sequencing ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Genome Sequencing ◽  
Metastatic Cancer ◽  
Whole Genome

scholarly journals Clinical outcomes after whole-genome sequencing in patients with metastatic non-small-cell lung cancer

2018 ◽  
Vol 5 (1) ◽  
pp. a002659
Author(s):  
Erica S. Tsang ◽  
Yaoqing Shen ◽  
Negar Chooback ◽  
Cheryl Ho ◽  
Martin Jones ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Whole Genome Sequencing ◽  
Clinical Outcomes ◽  
Genome Sequencing ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Whole Genome ◽  
Small Cell Lung
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