scholarly journals Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Wenbin Shen ◽  
Boer Shan ◽  
Shanhui Liang ◽  
Junling Zhang ◽  
Yangyang Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mutation Frequency ◽  
Advanced Ovarian Cancer ◽  
Circulating Tumor Dna ◽  
Cancer Tissue ◽  
Genomic Profiling ◽  
Tissue Samples ◽  
Hybrid Capture ◽  
Ovarian Cancer Tissue ◽  
Tumor Dna

Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases.Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N = 488) and the Cancer Genome Atlas (TCGA) database (N = 489).Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p < 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p < 0.05).Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.

scholarly journals Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel

2016 ◽  
Vol 8 ◽  
pp. BIC.S35775 ◽  
Author(s):  
Urmila Sehrawat ◽  
Ruchika Pokhriyal ◽  
Ashish Kumar Gupta ◽  
Roopa Hariprasad ◽  
Mohd Imran Khan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Spectrometric Analysis ◽  
Cancer Tissue ◽  
Chemotherapy Response ◽  
Tissue Samples ◽  
Post Surgery ◽  
Dismal Prognosis ◽  
Apoptotic Activity ◽  
Potential Biomarkers

Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response.

scholarly journals Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study

Tumor Biology ◽  
2020 ◽  
Vol 42 (5) ◽  
pp. 101042832091919 ◽  
Author(s):  
Mariana Cartaxo Alves ◽  
Fernando Luiz Affonso Fonseca ◽  
Alayne Magalhães Trindade Domingues Yamada ◽  
Lílian Arruda do Rego Barros ◽  
André Lopes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Early Response ◽  
Circulating Tumor Dna ◽  
Free Survival ◽  
Disease Free ◽  
Tumor Dna

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.

Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with advanced cancers of the GI tract and anus.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 618-618 ◽  
Author(s):  
Alexa Betzig Schrock ◽  
Lauren Young ◽  
Samuel Jacob Klempner ◽  
Rodolfo Bordoni ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Molecular Profiling ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Tissue Sampling ◽  
Gi Tract ◽  
Hybrid Capture ◽  
Non Invasive ◽  
Clinical Support ◽  
Average Maximum ◽  
Tumor Dna

618 Background: The treatment of GI carcinomas (CA) is influenced by the presence or absence of prognostic and predictive genomic alterations (GA). Tissue sampling is the historical platform for genomic biomarker assessment, but non-invasive ctDNA assay provides an alternative when tissue is unavailable or cannot be safely obtained. Methods: Hybrid-capture based genomic profiling using a ctDNA assay (FoundationACT) was performed on blood samples from 82 consecutive pts with lower alimentary canal CA. Results: Median age was 62 (range 28-92) and 61% were male. Anatomic breakdown included CRC (n = 51), esophageal (n = 9), gastric (n = 8), gastroesophageal (n = 3) and small bowel adenoCA (SBA, n = 2), anus squamous cell CA (n = 5), and other GI CA (n = 4). At least one GA was reported in 72% of cases. In 23 cases with no GA reported, the average maximum somatic allele frequency was 0.17% (95% CI: 0-0.6%) vs. 16.7% (95% CI: 0-54.4%) for the 59 cases with GAs (P < 0.0001). For the 3 of 18 patients with both blood and tissue testing performed and samples collected within a 30-day interval, 8/9 (89%) GA detected in tissue were also detected in ctDNA. An average of 1.7 GA/sample were detected in ctDNA. The most commonly altered genes were TP53 (61%), KRAS (24%), BRAF (10%) and PIK3CA (10%). Comparative analysis using the tissue-based Foundation Core database showed a similar trend with overall slightly higher frequencies of GAs in individual genes . RAF and RAS short variants (SV) were exclusive to lower GI and anal CA. KRAS and RAF1 amplification (amp) occurred only in esophageal CA (4/11, 36%). FGFR SV or amp was identified in 3 cases across the cohort. Of CRC, 4 (8%) had ≥ 1 ERBB2 activating SV or amp, 2 (4%) had IDH1/2 hotspot SV, and 2 (4%) had BRCA2 inactivating alterations. ERBB2 activating SV and EGFR amp were found in a SBA and an esophagus CA, respectively. A kinase fusion was identified as the sole driver in 1 CRC ( STRN-ALK) and 1 SBA ( GOPC-ROS1). Outcomes to targeted therapies will be presented for the available subset of patients. Conclusions: Our results provide early clinical support and confirm that hybrid-capture based ctDNA testing can reliably detect all 4 classes of GA and provide a molecular profiling option for patients with GI CA.

scholarly journals Detection of Somatic Mutation in Exon 12 of DNA Polymerase β in Ovarian Cancer Tissue Samples

2018 ◽  
Vol 22 (5) ◽  
pp. 355-359 ◽  
Author(s):  
Kalyani Khanra ◽  
Indranil Choudhuri ◽  
Nandan Bhattacharyya ◽  
◽  
◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Polymerase ◽  
Somatic Mutation ◽  
Cancer Tissue ◽  
Dna Polymerase Β ◽  
Tissue Samples ◽  
Ovarian Cancer Tissue

FISH analysis of BRCA1 copy number in paraffin-embedded ovarian cancer tissue samples

2004 ◽  
Vol 76 (2) ◽  
pp. 138-142 ◽  
Author(s):  
Hisanori Kato ◽  
Atsushi Arakawa ◽  
Kaoru Suzumori ◽  
Nobuhiko Kataoka ◽  
S.Robert Young
Keyword(s):  
Ovarian Cancer ◽  
Copy Number ◽  
Cancer Tissue ◽  
Fish Analysis ◽  
Tissue Samples ◽  
Ovarian Cancer Tissue

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced hepatocellular carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15606-e15606
Author(s):  
Mao Li ◽  
Ailin Wei ◽  
Wenzhuan Xie ◽  
Jing Zhao ◽  
Zhengyi Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circulating Tumor Dna ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Genomic Profiling ◽  
Promising Alternative ◽  
Hybrid Capture ◽  
Advanced Hcc ◽  
Tissue Biopsy ◽  
Tumor Dna

e15606 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a particularly high prevalence in China. The genomic profiling in HCC had been widely explored with tissue biopsy, however, given the intrinsic risks of invasive approach, blood-based circulating tumor DNA (ctDNA) has been proposed as a promising alternative. In this study, we aim to investigate whether the ctDNA may serve as a reliable tool to provide a more accurate molecular snapshot of HCC in Chinese patients. Methods: Plasma samples from 385 Chinese patients with advanced HCC were assayed for somatic genomic alternations by hybrid capture-based next-generation sequencing (NGS) with 150 genes and a mean sequencing depth of more than 3000×. The results were compared with our internal tissue genomic database of Chinese HCC patients (N = 873) tested by NGS and TCGA database (N = 373) tested by whole exome sequencing. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Results: Among 385 patients with ctDNA testing, somatic genomic alternations were detected in 97% of the patients (median = 5 alterations/patient). The most prevalent SNV mutations from ctDNA sequencing were TP53 (45.7%), TERT (19.5%), CTNNB1 (12.5%), and LRP1B (8.3%) compared to our tissue database (TP53 (61.2%), CTNNB1 (15.6%), TERT (13.3%), and LRP1B (11.0%)). While in TCGA database, the most common SNV mutations were found in TP53 (30.1%), CTNNB1 (26.0%), LRP1B (8.8%), ARID1A (8.6%), and SPTA1 (7.5%). Moreover, the level of MSAF was associated with detectable variant types, evidenced by a significant higher MSAF level observed when amplifications (P < 0.0001) or fusions (P = 0.008) were detected in the samples. Conclusions: Molecular analysis of patients with advanced HCC through ctDNA can serve as a reliable alternative to tissue biopsy. Chinese HCC patients may have different mutational landscapes to Western population. The utility of ctDNA analysis can provide therapeutically exploitable genomic profiles to identify potentially actionable gene alterations for targeted therapies.

scholarly journals LncRNA-MSC-AS1 inhibits the ovarian cancer progression by targeting miR-425-5p

2021 ◽  
Author(s):  
Yinling Zhao ◽  
Donglan Yuan ◽  
Dandan Zhu ◽  
Tianhui Xu ◽  
Aihua Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Cancer Tissue ◽  
Western Blot Assay ◽  
Tissue Samples ◽  
Ovarian Cancer Tissue ◽  
Skov3 Cells ◽  
Tumor Suppressive Function

Abstract Background Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were reported to be aberrantly expressed and related to the pathogenesis of ovarian cancer. However, the role and regulatory mechanism of MSC-AS1 in ovarian cancer has yet to be fully elucidated. Methods Expression of lncRNA MSC-AS1 (MSC-AS1) and microRNA-425-5p (miR-425-5p) in the ovarian cancer tissue samples and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The functions of MSC-AS1 on ovarian cancer cell proliferation, cell cycle and apoptosis were determined using MTT, colony formation and flow cytometry analyses. The protein expression levels were evaluated using western blot assay. The targeting relationship MSC-AS1 and miR-425-5p was verified via dual-luciferase reporter assay. Results MSC-AS1 expression level was lowly expressed, while miR-425-5p level was highly in ovarian cancer tissues and cells. Elevation of MSC-AS1 has the ability to significantly inhibit cell proliferation and facilitate cell apoptosis in SKOV3 cells. Moreover, MSC-AS1 targeted and negatively modulated miR-425-5p. MiR-425-5p up-regulation has been proved to partially reverse the tumor suppressive function of MSC-AS1 overexpression. Conclusion MSC-AS1 sponged miR-425-5p to inhibit the ovarian cancer progression. These findings may provide a promising therapeutic target for the treatment of ovarian cancer.

scholarly journals Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus

2018 ◽  
Vol 24 (8) ◽  
pp. 1881-1890 ◽  
Author(s):  
Alexa B. Schrock ◽  
Dean Pavlick ◽  
Samuel J. Klempner ◽  
Jon H. Chung ◽  
Brady Forcier ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Hybrid Capture ◽  
Tumor Dna

Optimization of aptamer selection on an automated microfluidic system with cancer tissues

Lab on a Chip ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 725-734
Author(s):  
Cheng-Sheng Lin ◽  
Yi-Cheng Tsai ◽  
Keng-Fu Hsu ◽  
Gwo-Bin Lee
Keyword(s):  
Ovarian Cancer ◽  
High Specificity ◽  
Microfluidic System ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Ovarian Cancer Tissue ◽  
Aptamer Selection ◽  
Cancer Tissues

Optimization of aptamer selection using tissue samples has been carried out on an automated microfluidic system and one screened aptamer exhibited high specificity and affinity towards ovarian cancer tissue.

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