GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Plasma-Based Measurements of Tumor Heterogeneity Correlate with Clinical Outcomes in Metastatic Colorectal Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 9 ( 2022-04-29), p. 2240-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 9 ( 2022-04-29), p. 2240-
    Abstract: Sequencing circulating tumor DNA (ctDNA) from liquid biopsies may better assess tumor heterogeneity than limited sampling of tumor tissue. Here, we explore ctDNA-based heterogeneity and its correlation with treatment outcome in STEAM, which assessed efficacy and safety of concurrent and sequential FOLFOXIRI-bevacizumab (BEV) vs. FOLFOX-BEV for first-line treatment of metastatic colorectal cancer. We sequenced 146 pre-induction and 89 post-induction patient plasmas with a 198-kilobase capture-based assay, and applied Mutant-Allele Tumor Heterogeneity (MATH), a traditionally tissue-based calculation of allele frequency distribution, on somatic mutations detected in plasma. Higher levels of MATH, particularly in the post-induction sample, were associated with shorter progression-free survival (PFS). Patients with high MATH vs. low MATH in post-induction plasma had shorter PFS (7.2 vs. 11.7 months; hazard ratio, 3.23; 95% confidence interval, 1.85–5.63; log-rank p 〈 0.0001). These results suggest ctDNA-based tumor heterogeneity may have potential prognostic value in metastatic cancers.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14092240
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Disease Monitoring Using Post-induction Circulating Tumor DNA Analysis Following First-Line Therapy in Patients with Metastatic Colorectal Cancer
    American Association for Cancer Research (AACR) ; 2020
    In:  Clinical Cancer Research Vol. 26, No. 15 ( 2020-08-01), p. 4010-4017
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 15 ( 2020-08-01), p. 4010-4017
    Abstract: We assessed plasma circulating tumor DNA (ctDNA) level as a prognostic marker for progression-free survival (PFS) following first-line metastatic colorectal cancer (mCRC) therapy. Experimental Design: The Sequencing Triplet With Avastin and Maintenance (STEAM) was a randomized, phase II trial investigating efficacy of bevacizumab (BEV) plus 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) and 5-fluorouracil/leucovorin/irinotecan (FOLFIRI), administered concurrently or sequentially, versus FOLFOX-BEV in first-line mCRC. Evaluation of biomarkers associated with treatment outcomes was an exploratory endpoint. Patients in the biomarker-evaluable population (BEP) had 1 tissue sample, 1 pre-induction plasma sample, and 1 post-induction plasma sample collected ≤60 days of induction from last drug date. Results: Among the 280 patients enrolled in STEAM, 183 had sequenced and evaluable tumor tissue, 118 had matched pre-induction plasma, and 54 (BEP) had ctDNA-evaluable sequencing data for pre- and post-induction plasma. The most common somatic variants in tumor tissue and pre-induction plasma were TP53, APC, and KRAS. Patients with lower-than-median versus higher-than-median post-induction mean allele fraction (mAF) levels had longer median PFS (17.7 vs. 7.5 months, HR, 0.33; 95% confidence interval, 0.17–0.63). Higher levels of post-induction mAF and post-induction mean mutant molecules per milliliter (mMMPM), and changes in ctDNA (stratified by a 10-fold or 100-fold reduction in mAF between pre- and post-induction plasma), were associated with shorter PFS. Post-induction mAF and mMMPM generally correlated with each other (ρ = 0.987, P & lt; 0.0001). Conclusions: ctDNA quantification in post-induction plasma may serve as a prognostic biomarker for mCRC post-treatment outcomes.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-19-1209
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 10 ( 2022-05-18), p. 2479-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 10 ( 2022-05-18), p. 2479-
    Abstract: Monitoring treatment efficacy early during therapy could enable a change in treatment to improve patient outcomes. We report an early assessment of response to treatment in advanced NSCLC using a plasma-only strategy to measure changes in ctDNA levels after one cycle of chemotherapy. Plasma samples were collected from 92 patients with Stage IIIB-IV NSCLC treated with first-line chemo- or chemoradiation therapies in an observational, prospective study. Retrospective ctDNA analysis was performed using next-generation sequencing with a targeted 198-kb panel designed for lung cancer surveillance and monitoring. We assessed whether changes in ctDNA levels after one or two cycles of treatment were associated with clinical outcomes. Subjects with ≤50% decrease in ctDNA level after one cycle of chemotherapy had a lower 6-month progression-free survival rate (33% vs. 58%, HR 2.3, 95% CI 1.2 to 4.2, log-rank p = 0.009) and a lower 12-month overall survival rate (25% vs. 70%, HR 4.3, 95% CI 2.2 to 9.7, log-rank p 〈 0.001). Subjects with ≤50% decrease in ctDNA level after two cycles of chemotherapy also had shorter survival. Using non-invasive liquid biopsies to measure early changes in ctDNA levels in response to chemotherapy may help identify non-responders before standard-of-care imaging in advanced NSCLC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14102479
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Characterizing Cas9 Protospacer-Adjacent Motifs with High-Throughput Sequencing of Library Depletion Experiments
    Cold Spring Harbor Laboratory ; 2016
    In:  Cold Spring Harbor Protocols Vol. 2016, No. 5 ( 2016-05), p. pdb.prot090183-
    Details
    In: Cold Spring Harbor Protocols, Cold Spring Harbor Laboratory, Vol. 2016, No. 5 ( 2016-05), p. pdb.prot090183-
    Abstract: This protocol outlines a general approach for characterizing the protospacer-adjacent motifs (PAMs) of Cas9 orthologs. It uses a three-plasmid system: One plasmid carries Cas9 and its tracrRNA, a second targeting vector contains the spacer and repeat, and the third plasmid encodes the targeted sequence (as the protospacer) with varying PAM sequences. It leverages the Cas9 nuclease activity to cleave and destroy plasmids that bear a compatible PAM. The level of depletion of a library of targeted plasmids after Cas9-mediated selection can then be assessed by deep sequencing to reveal candidate PAMs for downstream validation.
    Type of Medium: Online Resource
    ISSN: 1940-3402 , 1559-6095
    URL: Article
    DOI: 10.1101/pdb.prot090183
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2016
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Orthogonal Cas9 proteins for RNA-guided gene regulation and editing
    Springer Science and Business Media LLC ; 2013
    In:  Nature Methods Vol. 10, No. 11 ( 2013-11), p. 1116-1121
    Details
    In: Nature Methods, Springer Science and Business Media LLC, Vol. 10, No. 11 ( 2013-11), p. 1116-1121
    Type of Medium: Online Resource
    ISSN: 1548-7091 , 1548-7105
    URL: Article
    DOI: 10.1038/nmeth.2681
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2163081-1
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Evaluation of clonal hematopoiesis in late stage NSCLC using a next-generation sequencing panel targeting cancer genes.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 9050-9050
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 9050-9050
    Abstract: 9050 Background: Somatic mutations derived from the expansion of clonal populations of blood cells (clonal hematopoiesis of indeterminate potential, or CHIP) may be detected in sequencing of cell-free DNA (cfDNA) samples. We evaluated the potential implications of CHIP in targeted sequencing of lung cancer plasma samples using matched peripheral blood mononuclear cells (PBMC) to identify CHIP. Methods: Samples were evaluated from OAK, a phase 3 trial of atezolizumab in locally advanced or metastatic NSCLC following failure with platinum-based therapy. 94 samples from Cycle 1 Day 1 (C1D1) plasma and matched PBMC were analyzed with the AVENIO ctDNA Surveillance Kit (For Research Use Only, not for use in diagnostic procedures), a 198-kb next-generation sequencing panel targeting cancer genes. Plasma samples from subsequent cycles of therapy (C2D1, C3D1, and C4D1) were also sequenced with the same panel. Using median input amounts of 22.8 ng cfDNA and 50 ng PBMC DNA, we obtained median deduplicated depths of 5413 and 5070, respectively. Results: In C1D1 cfDNA, a median of 120 single nucleotide variants were detected per sample, with 5.13% of variants not identified in matched PBMC (i.e., putative tumor-derived somatic variants) versus 94.87% of variants identified in matched PBMC (i.e., germline or CHIP variants). While the majority of PBMC-matched variants were SNPs with allele frequency (AF) around 50% or 100% as expected, there was a median of 1 (range 0-8) PBMC-matched cfDNA variants per sample with AF below 10%. Consistent with CHIP, the number of PBMC-matched cfDNA variants per subject below AF 10% were positively associated with age (p-value = 0.0145), and TP53 was the most frequently mutated gene. We found similar results in plasma samples from subsequent cycles. Conclusions: Plasma and PBMC sequencing analysis identified potential mutations derived from CHIP. However, 39% of cfDNA samples had zero potential CHIP mutations identified in the study, possibly due to the specific regions targeted by the AVENIO assay. While this study suggests that only a small percentage of variants detected by the AVENIO Surveillance panel in lung cancer are derived from CHIP, further studies are warranted to assess the impact and removal of these variants.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.9050
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Improving microbial fitness in the mammalian gut by in vivo temporal functional metagenomics
    EMBO ; 2015
    In:  Molecular Systems Biology Vol. 11, No. 3 ( 2015-03)
    Details
    In: Molecular Systems Biology, EMBO, Vol. 11, No. 3 ( 2015-03)
    Abstract: image A platform for mining metagenomic DNA for genes contributing to fitness of commensal bacteria in vivo is presented. TFUM seq (Temporal FU nctional Metagenomics sequencing) uses shotgun libraries cloned into a recipient bacterial species, tracked over time in gnotobiotic mice by deep sequencing and computational methods. TFUM seq highlights the utility of functional metagenomics for engineering commensal bacteria with improved properties, including expanded colonization capabilities in vivo . Genes from a donor commensal bacterial species, Bacteroides thetaiotaomicron, confer fitness advantages to E. coli growing in the mouse gut. Analyses of population dynamics of E. coli clones harboring Bacteroides thetaiotaomicron genes reveals a galactokinase central to early colonization of the mouse gut, and subsequent dominance of a glycoside hydrolase enabling sucrose metabolism in E. coli . Co‐evolution of the donor plasmid library and the E. coli genome occurs, driving increased galactose utilization in E. coli .
    Type of Medium: Online Resource
    ISSN: 1744-4292 , 1744-4292
    URL: Article
    DOI: 10.15252/msb.20145866
    Language: English
    Publisher: EMBO
    Publication Date: 2015
    detail.hit.zdb_id: 2193510-5
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Incorporating Genetic Biomarkers in WHO Classification of Lung Cancer
    Elsevier BV ; 2022
    In:  Journal of Thoracic Oncology Vol. 17, No. 9 ( 2022-09), p. e79-e80
    Details
    In: Journal of Thoracic Oncology, Elsevier BV, Vol. 17, No. 9 ( 2022-09), p. e79-e80
    Type of Medium: Online Resource
    ISSN: 1556-0864
    URL: Article
    DOI: 10.1016/j.jtho.2022.04.007
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2223437-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Evaluation of a regularly updated knowledge base for curation of somatic mutations detected in whole exomes of melanoma and lung, colorectal, and breast cancers.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e14072-e14072
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e14072-e14072
    Abstract: e14072 Background: Evolving medical guidelines and complex multi-variant data from next-generation sequencing (NGS) testing of cancer samples make routine clinical interpretation of somatic variants challenging. We assessed the ability of NAVIFY(R) Mutation Profiler*, a CE-IVD somatic variant interpretation tool, to yield accurate time- and geography-specific clinical content on 2511 samples from The Cancer Genome Atlas (TCGA) across six solid tumor types. Methods: Whole exomes from lung adenocarcinoma (n = 469), lung squamous cell carcinoma (n = 325), colon adenocarcinoma (n = 368), rectum adenocarcinoma (n = 149), breast invasive carcinoma (n = 806), and skin cutaneous melanoma (n = 394) cases were analyzed. We utilized TCGA data from the Multi-Center Mutation Calling in Multiple Cancers (MC3) project to obtain consensus calling results of single nucleotide variants and indels. The open-access Mutation Annotation Format (MAF) file (v0.2.8) that stores variant calls was lifted to human reference genome GRCh38 and converted to individual Variant Call Format (VCF) files per case. VCF files were uploaded to NAVIFY Mutation Profiler to interpret actionable mutations according to a highly curated and up-to-date knowledge base (Roche Content v2.13.0 released December 6, 2019). We further assessed the accuracy of interpreting co-occurrences of actionable mutations. Results: Over 1.24 million somatic mutations across 20,590 genes were assessed with NAVIFY Mutation Profiler, which reported tier classifications of variants based on consensus recommendations from AMP, ASCO, CAP, and ACMG. 86% of cases had variants of strong (Tier I-A or I-B) or potential (Tier II-C or II-D) clinical significance; 56% of these cases had Tier I classifications, supported by robust clinical evidence. Potentially actionable variant-variant interactions were found in 14% of cases. The tool also identified appropriate tier classifications by geographic region in accordance with local medical guidelines. Conclusions: To benchmark against other tools, we utilized available exome data from TCGA MC3 to assess NAVIFY Mutation Profiler. While this study likely underestimates the fraction of cases with actionable mutations, given that copy number alterations or rearrangements are also present in TCGA samples, we found a higher yield of potentially actionable annotation than other published methods. * This product has not been evaluated by the Food and Drug Administration and is not commercially available in the United States.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e14072
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Disease monitoring and TKI resistance mutations of EGFR mutation-positive NSCLC patients via circulating tumor DNA.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21627-e21627
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21627-e21627
    Abstract: e21627 Background: 15–40% of NSCLC adenocarcinoma patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify tumor associated somatic EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression, to assess therapeutic response, and to identify resistance mechanisms. Methods: 106 longitudinal plasma samples from 16 NSCLC patients who were treated with osimertinib as either first line or second line therapy were collected. A series of plasma samples collected during treatment and at the time of disease progression were analyzed with the AVENIO ctDNA Surveillance kit*. Mutations at each time point were identified and reported by the AVENIO software v2.0*. The mutation profile of each patient at different timepoints along with the treatment journey was examined in combination with clinical outcome data. Results: EGFR sensitizing mutations were detected in all plasma samples by sequencing except in 3 cases. Patients responsive to anti-EGFR therapy showed a rapid decrease of EGFR driver mutations to non-detectable levels. Meanwhile, patients who had stable disease or rapid disease progression had stable or slightly decreasing ctDNA levels after receiving the treatment. One patient had a MET amplification, FBXL7 SNV, and EGFR T790M detected at the time of disease progression which were not detected at baseline. One patient had both EGFR L858R and T790M mutations. This patient progressed very quickly on erlotinib. Detection of the T790M mutation decreased upon osimertinib administration, however, the L858R mutation level stayed the same. TP53 mutations were elevated in 3 patients at the time of progression, and could potentially be related to anti-EGFR resistance. Conclusions: This study clearly demonstrated that liquid biopsy could identify resistance mutations beyond EGFR prior to clinical progression. Plasma samples collected prior to or at disease progression could facilitate identification of novel resistant mutations to TKI therapy. Further studies to demonstrate the clinical utility of serial blood EGFR testing in NSCLC management are necessary. *For Research Use Only. Not for use in diagnostic procedures.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21627
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...