scholarly journals The mutational landscape of spinal chordomas and their sensitive detection using circulating tumor DNA

2020 ◽  
Author(s):  
Austin K Mattox ◽  
Beibei Yang ◽  
Christopher Douville ◽  
Sheng-fu Lo ◽  
Daniel Sciubba ◽  
...  
Keyword(s):  
Clinical Status ◽  
Spinal Column ◽  
Disease Recurrence ◽  
The United States ◽  
Circulating Tumor Dna ◽  
Blood Draw ◽  
Primary Tumors ◽  
Whole Exome ◽  
Tumor Dna

Abstract Background Chordomas are the most common primary spinal column malignancy in the United States. The aim of this study was to determine whether chordomas may be detected by evaluating mutations in circulating tumor DNA (ctDNA). Methods 32 patients with a biopsy-confirmed diagnosis of chordoma had blood drawn pre-operatively and/or at follow up appointments. Mutations in the primary tumor were identified by whole exome sequencing and liquid biopsy by ddPCR and/or RACE-Seq was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. Results 87.1% of patients were ctDNA positive at the time of initial blood draw (p < 0.001). Follow up blood draws in twenty of the patients suggest that ctDNA levels may reflect the clinical status of the disease. Patients with positive ctDNA levels were more likely to have greater mutant allele frequencies in their primary tumors (p = 0.004) and undergo radiotherapy (p = 0.02), and the presence of ctDNA may correlate with response to systemic chemotherapy and/or disease recurrence. Conclusions Detection of ctDNA mutations may allow for the detection and monitoring of disease progression for chordomas.

scholarly journals GENE-01. THE MUTATIONAL LANDSCAPE OF PRIMARY CHORDOMAS AND THEIR SENSITIVE DETECTION IN PLASMA ctDNA BY MULTIPLE NEXT GENERATION SEQUENCING TECHNOLOGIES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Austin Mattox ◽  
Yuchen Jiao ◽  
Cherie Blair ◽  
Nickolas Papadopoulos ◽  
Chetan Bettegowda
Keyword(s):  
Liquid Biopsy ◽  
Clinical Status ◽  
Spinal Column ◽  
Digital Pcr ◽  
Disease Recurrence ◽  
Blood Draw ◽  
Tumor Seeding ◽  
Mutational Landscape ◽  
Sequencing Technologies

Abstract CNS-associated tumors are notoriously difficult to detect in plasma. Chordomas are the most common primary spinal column malignancy, and extensive surgical procedures, along with chemotherapy and radiation are required to reduce recurrence. Currently CT, MRI, and PET are used to monitor for recurrence but are limited by surgical sequalae. In addition, needle biopsy risks tumor seeding along the biopsy track. In the largest cohort of chordomas described thus far, we characterize the mutational landscape of these tumors and show that liquid biopsy is a sensitive method for detecting cancers. 34 patients with a biopsy-confirmed diagnosis of chordoma had blood drawn before surgery, at the time of surgery, and/or at follow up appointments. Mutations in the primary tumor were identified by whole exome sequencing (WES) and droplet digital PCR (ddPCR) and/or Rapid Amplification of cDNA Ends Sequencing (RACE-Seq) was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. The primary endpoint was detection of mutations in ctDNA in biopsy-confirmed chordoma samples. 87.9% of patients were ctDNA positive at the time of initial blood draw (p < 0.001). Follow up blood draws in twenty of the patients demonstrated that ctDNA levels reflected the clinical status of the disease. Patients with positive ctDNA levels were more likely to undergo radiotherapy (p = 0.004), and the presence of ctDNA may predict response to systemic chemotherapy and/or disease recurrence. Given the significant sequelae of biopsy and spinal surgery, liquid biopsy may be the best tool for detection and monitoring of chordomas.

scholarly journals Serial Circulating Tumor DNA Identification Associated with the Efficacy and Prognosis of Neoadjuvant Chemotherapy in Breast Cancer

2021 ◽  
Author(s):  
Yidong Zhou ◽  
Yaping Xu ◽  
Changjun Wang ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Circulating Tumor Dna ◽  
College Hospital ◽  
Primary Tumors ◽  
Blood Samples ◽  
Tumor Dna

Abstract Background: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. Methods: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1,021-gene panel. Results: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, one versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904–290.9; p < 0.0001). Conclusions: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient survival. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome.Trial registration: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).

scholarly journals Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anaïs Prouteau ◽  
Jérôme Alexandre Denis ◽  
Pauline De Fornel ◽  
Edouard Cadieu ◽  
Thomas Derrien ◽  
...  
Keyword(s):  
Residual Disease ◽  
Specific Antigen ◽  
Point Mutations ◽  
Antigen Receptor ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Histiocytic Sarcoma ◽  
Oncology Research ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

scholarly journals PATH-06. ASSESSMENT OF CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID BY WHOLE EXOME SEQUENCING TO DETECT GENOMIC ALTERATIONS OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii165-ii165
Author(s):  
Hao Duan ◽  
Zhenqiang He ◽  
Zhenghe Chen ◽  
Yonggao Mou
Keyword(s):  
Cerebrospinal Fluid ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Whole Exome ◽  
Resected Tumor ◽  
Tumor Dna

Abstract Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF comparing with the corresponding tumor tissue samples (3.56±0.75 vs. 2.22±0.32, P=0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.12% ± 6.03% vs. 73.83% ± 5.95%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3F3A which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

scholarly journals Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Matthew L. Hemming ◽  
Kelly Klega ◽  
Justin Rhoades ◽  
Gavin Ha ◽  
Kate E. Acker ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Size ◽  
Disease Burden ◽  
Progressive Disease ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

Purpose Leiomyosarcoma (LMS) is a soft-tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single-nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease. Patients and Methods We evaluated cell-free DNA in plasma samples and paired genomic DNA from resected tumors from patients with LMS by ultra-low passage whole-genome sequencing. Sequencing reads were aligned to the human genome and CNAs that were identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features. Results We identified LMS ctDNA in 11 (69%) of 16 patients with disease progression and total tumor burden greater than 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined after resection of progressive disease in one case and became detectable upon disease relapse in another individual patient. Conclusion These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of patients with uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence, and differentiating benign and malignant smooth muscle tumors.

scholarly journals Plasma circulating tumor DNA in pancreatic adenocarcinoma for screening, diagnosis, prognosis, treatment and follow-up: A systematic review

2020 ◽  
Vol 87 ◽  
pp. 102028 ◽  
Author(s):  
Raëf Abdallah ◽  
Valérie Taly ◽  
Shulin Zhao ◽  
Daniel Pietrasz ◽  
Jean-Baptiste Bachet ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Adenocarcinoma ◽  
Circulating Tumor Dna ◽  
Tumor Dna
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