scholarly journals Faculty Opinions recommendation of Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary.

2019 ◽  
Author(s):  
Steve Plaxe
Keyword(s):  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Unknown Primary ◽  
Carcinoma Of Unknown Primary ◽  
Tumor Dna

scholarly journals Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary

2017 ◽  
Vol 77 (16) ◽  
pp. 4238-4246 ◽  
Author(s):  
Shumei Kato ◽  
Nithya Krishnamurthy ◽  
Kimberly C. Banks ◽  
Pradip De ◽  
Kirstin Williams ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Unknown Primary ◽  
Carcinoma Of Unknown Primary ◽  
Tumor Dna

Genomic analysis of circulating tumor DNA in 442 patients with carcinoma of unknown primary: Implications for targeted therapeutics.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11511-11511
Author(s):  
Shumei Kato ◽  
Nithya Krishnamurthy ◽  
Kimberly Banks ◽  
Kirstin Anne Williams ◽  
Casey B. Williams ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Unknown Primary ◽  
Next Generation ◽  
Single Nucleotide Variants ◽  
Dynamic Changes ◽  
Carcinoma Of Unknown Primary ◽  
Molecular Alterations ◽  
Tumor Dna

11511 Background: Carcinoma of unknown primary (CUP) is a rare, difficult-to-treat malignancy. To further understand the genomic landscape of CUP, next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from patient plasma was performed. To our knowledge, this is the largest cohort of patients with CUP interrogated by liquid biopsy. Methods: We evaluated the molecular alterations of 442 patients with CUP using clinical-grade NGS of ctDNA isolated from patient plasma. The test detects single nucleotide variants in 54-70 genes, as well as copy number amplifications, fusions and indels in selected genes. Results: Eighty percent of patients (353/442) had ctDNA alterations with 66% (290/442) harboring at least one characterized alteration; 43.9% (194/442) ≥ 2 characterized alterations. TP53-associated genes were most commonly altered (37.8% [167/442]) followed by genes involved in the MAPK pathway (31.2% [138/442]), PI3K signaling (18.1% [80/442]) and the cell cycle machinery (10.4% [46/442]). Among patients harboring at least one characterized alteration, most (87.9% [255/290]) had distinct genomic profiles, and 99.7% (289/290) had alterations theoretically targetable with either an FDA-approved or investigational agent. The mean number of potentially actionable alterations per patient was 1.7 (range, 0 to 10). Illustrative patients who had dynamic changes in ctDNA content during the course of therapy and responding patients matched on the basis of ctDNA to targeted therapies or immunotherapy will be presented. Conclusions: Evaluation of ctDNA was feasible among individuals with CUP. Most patients harbored a unique somatic profile. The majority of patients had potentially actionable alterations. Serial ctDNA showed dynamic changes in molecular alterations in response to therapy, and several patients have attained responses to targeted or immune therapies chosen on the basis of ctDNA findings. The current report suggests that non-invasive liquid biopsies merit investigation in next generation clinical trials.

Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 25-25
Author(s):  
Hanna Tukachinsky ◽  
Russell Madison ◽  
Jon Chung ◽  
Lucas Dennis ◽  
Bernard Fendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Acquired Resistance ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Cancer Tissue ◽  
Castration Resistant Prostate Cancer ◽  
High Level ◽  
Tumor Dna

25 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from plasma provides a minimally invasive method to identify targetable genomic alterations (GAs) and resistance mechanisms in patients with metastatic castration-resistant prostate cancer (mCRPC). The circulating tumor fraction in patients with mCRPC and the clinical validity of GAs detected in plasma remain unknown. We evaluated the landscape of GAs using ctDNA-based CGP and assessed concordance with tissue-based CGP. Methods: Plasma from 3,334 patients with advanced prostate cancer (including 1,674 mCRPC screening samples from the TRITON2/3 trials and 1,660 samples from routine clinical CGP) was analyzed using hybrid-capture-based gene panel NGS assays. Results were compared with CGP of 2,006 metastatic prostate cancer tissue biopsies. Concordance was evaluated in 837 patients with both tissue (archival or contemporaneous) and plasma NGS results. Results: 3,127 patients [94%] had detectable ctDNA. BRCA1/2 were mutated in 295 patients [8.8%]. In concordance analysis, 72/837 [8.6%] patients had BRCA1/2 mutations detected in tissue, 67 [93%] of whom were also identified by ctDNA, and 20 patients were identified using ctDNA but not tissue [23% of all patients identified using ctDNA]. ctDNA detected subclonal BRCA1/2 reversions in 10 of 1,660 [0.6%] routine clinical CGP samples. AR alterations, including amplifications and hotspot mutations, which were detected in 940/2,213 patients [42%]. Rare AR compound mutations, rearrangements, and novel in-frame deletions were identified. Altered pathways included PI3K/AKT/mTOR [14%], WNT/β-catenin [17%], and RAS/RAF/MEK [5%]. Microsatellite instability was detected in 31/2,213 patients [1.4%]. Conclusions: In the largest study of mCRPC plasma samples conducted to date, CGP of ctDNA recapitulated the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 alterations. It also identified patients who may have gained somatic BRCA1/2 alterations since archival tissue was collected. ctDNA detected more acquired resistance GAs than tissue, including novel AR-activating variants. The large percentage of patients with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations position liquid biopsy as a compelling clinical complement to tissue CGP for patients with mCRPC.

scholarly journals Genomic Analysis of Circulating Tumor DNA Using a Melanoma-Specific UltraSEEK Oncogene Panel

2019 ◽  
Vol 21 (3) ◽  
pp. 418-426 ◽  
Author(s):  
Elin S. Gray ◽  
Tom Witkowski ◽  
Michelle Pereira ◽  
Leslie Calapre ◽  
Karl Herron ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Tumor Dna

Circulating tumor DNA molecular profiling in rare cancer patients from the MASTER KEY Project.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14532-e14532
Author(s):  
Hitomi Sumiyoshi Okuma ◽  
Kan Yonemori ◽  
Takuji Seo ◽  
Emi Noguchi ◽  
Keiko Wakakuwa ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Salivary Gland Tumor ◽  
Circulating Tumor Dna ◽  
Genetic Alterations ◽  
Unknown Primary ◽  
Genomic Alteration ◽  
Cancer Type ◽  
Rare Cancer ◽  
Registry Study ◽  
Tumor Dna

e14532 Background: In April 2017, MASTER KEY Project, composed of a prospective registry study part and a multiple clinical trials part, was established to promote treatment development for rare cancers, which is lacking standard or investigational therapeutic options. Circulating tumor DNA (ctDNA) analysis by next-generation sequencing (NGS) has provided new insight into personalized medicine in a more accessible, non-invasive manner; however, most reports are focused on common cancers. We report genetic alterations detected by ctDNA NGS analysis in rare solid cancers. Methods: Prospectively consented patients (pts), also enrolled in MASTER KEY registry study, had ctDNA NGS testing at a CLIA-certified lab (Guardant360) for point mutations, indels, copy number amplifications, fusions, and microsatellite instability. Alterations were assessed for incidence according to cancer type, functional impact, therapeutic implications, and comparison with tissue NGS. Main inclusion criteria: 1) age ≥16, 2) histological diagnosis of rare cancer (annual incidence less than 6 cases per 100,000 population), cancer of unknown primary (CUP), or rare tissue subtypes of common cancers, 3) active metastatic / unresectable cancer, 4) a written consent. Results: From Nov. 2018 to Jan 2019, 50 pts had Guardant360 testing. Diseases included: soft tissue sarcoma (28), ovarian carc. (7), CUP (4), salivary gland tumor (3), thyroid carc. (2), GIST (1), adrenal cortical carc. (1), rare subtype of GI tract (1), malignant mesothelioma (1), nephroblastoma (1), NET (1), NUT carc. (1). All Japanese, male/female = 14/36, median age 61, ECOG performance status 0/1/2/3 = 30/19/0/1. 76% of pts (38/50) had ≥1 alteration detected, with median number of 2 alterations (range: 0-9), with VAF(0.1-60.3%); 87%(33/38) of those pts had a variant most likely pathogenic; 61% (20/33) of those pts had a variant potential for clinical action. Mean TAT was 10.3 days. 19 pts had tissue NGS testing and in 3 pts, alterations were detected by ctDNA NGS but not by tissue NGS. Updated results of 100 patients will be presented at the conference. Conclusions: Most rare cancer patients with advanced disease had a detectable genomic alteration by Guardant360. Clinical trial information: UMIN000034394.

scholarly journals Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms

2021 ◽  
pp. clincanres.CCR-20-4805-E.2020 ◽  
Author(s):  
Hanna Tukachinsky ◽  
Russell W. Madison ◽  
Jon H. Chung ◽  
Ole Gjoerup ◽  
Eric A Severson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Tumor Dna

scholarly journals Analysis of cell-free circulating tumor DNA in 419 patients with glioblastoma and other primary brain tumors

CNS Oncology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. CNS34 ◽  
Author(s):  
David E Piccioni ◽  
Achal Singh Achrol ◽  
Lesli A Kiedrowski ◽  
Kimberly C Banks ◽  
Najee Boucher ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Single Nucleotide Variants ◽  
Viable Option ◽  
Single Nucleotide ◽  
Primary Brain Tumors ◽  
Somatic Alteration ◽  
Tumor Sequencing ◽  
Tumor Dna

Aim: Genomically matched trials in primary brain tumors (PBTs) require recent tumor sequencing. We evaluated whether circulating tumor DNA (ctDNA) could facilitate genomic interrogation in these patients. Methods: Data from 419 PBT patients tested clinically with a ctDNA NGS panel at a CLIA-certified laboratory were analyzed. Results: A total of 211 patients (50%) had ≥1 somatic alteration detected. Detection was highest in meningioma (59%) and gliobastoma (55%). Single nucleotide variants were detected in 61 genes, with amplifications detected in ERBB2, MET, EGFR and others. Conclusion: Contrary to previous studies with very low yields, we found half of PBT patients had detectable ctDNA with genomically targetable off-label or clinical trial options for almost 50%. For those PBT patients with detectable ctDNA, plasma cfDNA genomic analysis is a clinically viable option for identifying genomically driven therapy options.

scholarly journals Enhanced detection of circulating tumor DNA by fragment size analysis

2018 ◽  
Vol 10 (466) ◽  
pp. eaat4921 ◽  
Author(s):  
Florent Mouliere ◽  
Dineika Chandrananda ◽  
Anna M. Piskorz ◽  
Elizabeth K. Moore ◽  
James Morris ◽  
...  
Keyword(s):  
Copy Number ◽  
Fragment Size ◽  
Area Under The Curve ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Biological Properties ◽  
Size Analysis ◽  
Plasma Samples ◽  
Tumor Dna

Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90 and 150 bp and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90 and 150 bp improved detection of tumor DNA, with more than twofold median enrichment in >95% of cases and more than fourfold enrichment in >10% of cases. Analysis of size-selected cfDNA identified clinically actionable mutations and copy number alterations that were otherwise not detected. Identification of plasma samples from patients with advanced cancer was improved by predictive models integrating fragment length and copy number analysis of cfDNA, with area under the curve (AUC) >0.99 compared to AUC <0.80 without fragmentation features. Increased identification of cfDNA from patients with glioma, renal, and pancreatic cancer was achieved with AUC > 0.91 compared to AUC < 0.5 without fragmentation features. Fragment size analysis and selective sequencing of specific fragment sizes can boost ctDNA detection and could complement or provide an alternative to deeper sequencing of cfDNA.

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