Clinical value of Next Generation Sequencing in Chinese pediatric soft tissue sarcoma: A multicenter data.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22005-e22005
Author(s):  
Suying Lu ◽  
Feifei Sun ◽  
Xiuli Yuan ◽  
Junting Huang ◽  
Juan Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Genomic Analysis ◽  
Parp Inhibition ◽  
Cancer Center ◽  
Next Generation ◽  
Clinical Value ◽  
Mesenchymal Tumors ◽  
Generation Sequencing

e22005 Background: To uncover the genomic characteristics as well as to, within the scope of pediatric soft tissue sarcoma (psts), assess the clinical value of Next Generation Sequencing (NGS), we present the first report of genomic profiles in Chinese psts. Methods: Tumor tissue, as well as peripheral blood from 41 psts patients, were collected in Sun Yat-Sen University Cancer Center, Shenzhen Children's Hospital and Nanfang Hospital. Samples were sequenced in a CLIA/CAP-accredited laboratory with a targeted NGS panel (Onco PanScan plus; GenetronHealth.inc) consisted of all exons of 831 cancer-related genes and mRNA of 395 genes. Bioinformatics analysis was conducted using a build-in computational pipeline. Results: A total of 41 samples consisted of five major histology types including rhabdomyosarcoma (RMS) (n = 11), fibrosarcoma (n = 4), Ewing's sarcoma (n = 4), INI1-deficient mesenchymal tumor (n = 4), and other mesenchymal tumors (n = 18). All patients were with doubtful diagnosis,advanced, relapsed, or refractory sarcoma, of which 85% samples were from initial diagnoses. In totally, we identified 116 somatic aberrations and 4 pathogenic or likely pathogenic germline mutations, with a median tumor mutational burden of 0.47/Mb (0–6.57). Genomic analysis revealed frequent alterations in TP53 (10%), NTRK fusion (10%), PAX3/7 fusion (8%), and ARID1A (7%). ARID1A (18% vs. 0%) and TP53 (18% vs. 3%) mutations were found with higher frequency compared with pediatric RMS data in a previous study (Jack et al 2014). ARID1A mutation was only reported in a RMS case report (Cramer et al 2017). Furthermore, the mutation of ARID1A potentially match PARP inhibitors, which may provide more therapeutic options. In addition, NGS aided pathologic diagnosis in 63% (26/41) patients. The proportion of confirmed diagnosis, differential diagnosis, and the excluded diagnosis was 41.5%, 12.2%, and 9.7%, respectively. Druggable alterations were detected in 39% patients (Table). Four patients received the treatment recommended by genetic testing, three of them with NTRK fusion were recruited in a matched clinical trial could be evaluated and showed partial remission upon Larotrectinib. Conclusions: We discovered ARID1A mutations, which potentially sensitive to PARP-inhibition, were at a higher incidence in Chinese RMS. This study demonstrated the value of NGS test in guiding the clinical practice of psts in Chinese population. [Table: see text]

scholarly journals Next Generation Sequencing Reveals Pathogenic and Actionable Genetic Alterations of Soft Tissue Sarcoma in Chinese Patients: A Single Center Experience

2021 ◽  
Vol 20 ◽  
pp. 153303382110689
Author(s):  
Gu Jin ◽  
Chunyang Wang ◽  
Dongdong Jia ◽  
Wenkang Qian ◽  
Chunming Yin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Clinical Test ◽  
Next Generation ◽  
Single Center ◽  
Single Center Experience ◽  
Generation Sequencing

Background: Next generation sequencing (NGS) has systematically investigated the genomic landscape of soft tissue sarcoma (STS) in Western patients, but few reports have described the utility of NGS in identifying pathogenic and targetable mutations in Asian patients. Methods: We review our single center experience of identifying the genomic profile and feasible genetic mutations in 65 Chinese patients with STS by NGS. Results: On average, 3.35 mutations were identified per patient (range, 0-28), and at least one mutation could be detected in 95.4% (62/65) of patients. TP53, MDM2, CDK4, KDR, and NF1 were the most frequent mutation genes in Chinese STS patients. Actionable mutations were discovered in 36.9% (24/65) of patients, and clinical benefit was achieved in 4 patients treated with corresponding molecular targeted therapies. Conclusions: Our study describes the mutation profile of Chinese STS patients by a single center experience. Some patients have achieved improved clinical outcomes by adopting treatment based on the results of genetic testing. NGS may affect clinical decision-making as a routine clinical test for patients with STS.

The clinical utility of next-generation sequencing for bone and soft tissue sarcoma

2021 ◽  
pp. 1-7
Author(s):  
Charles A. Gusho ◽  
Mia C. Weiss ◽  
Linus Lee ◽  
Steven Gitelis ◽  
Alan T. Blank ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Clinical Utility ◽  
Next Generation ◽  
Generation Sequencing

Targeted next generation sequencing of sarcomas for identification of therapeutic targets.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10577-10577
Author(s):  
Vinod Ravi ◽  
Siraj M. Ali ◽  
Naveen Ramesh ◽  
Funda Meric-Bernstam ◽  
Gary A. Palmer ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Current Knowledge ◽  
Ffpe Tissue ◽  
Cancer Center ◽  
Significant Heterogeneity ◽  
Next Generation ◽  
Mesenchymal Tumors ◽  
Genomic Alterations ◽  
Illumina Hiseq ◽  
Generation Sequencing

10577 Background: Sarcomas are a diverse group of mesenchymal tumors with significant heterogeneity. Evolving personalized cancer care strategies require identification of recurrent genomic alterations that can be targeted therapeutically. Due to the rarity of these tumors and lack of fresh or frozen tissue in routine clinical practice, DNA sequencing has been a challenge. Objective: To demonstrate the feasibility of a next-generation sequencing (NGS) platform that utilizes archival formalin-fixed paraffin-embedded (FFPE) tissue to evaluate the spectrum of DNA alterations seen in sarcomas. Methods: Study population included 35 consecutive patients with advanced sarcoma presenting to the sarcoma center at MD Anderson Cancer Center beginning August 2012 with archival FFPE tissue available for NGS. DNA was extracted from FFPE samples and used for hybridization capture and NGS on the Illumina HiSeq 2000 platform. A total of 182 cancer-associated genes and 37 introns of 14 commonly rearranged genes were evaluated for genomic alterations. In the absence of an individual–matched normal control, germline variations were removed using dbSNP and the remaining variants were classified on the basis of current knowledge of specific variants from cancer databases such as COSMIC. Results: 35 patients (10 Angiosarcomas, 9 Leiomyosarcomas, 3 synovial sarcomas, 13 other subtypes) underwent DNA extraction with a median yield of 3376 ng tumor DNA. The average sequencing depth was >900X. 43% of patients had point mutations/indels previously described in COSMIC and/or in known mutation hotspots. 54% of patients showed structural variants such as amplifications, deletions or rearrangements. 68% of genomic alterations are in genes that are actionable. We identified an apparently novel variant in KDR T771R in 2/10 patients with angiosarcoma. KDR amplifications were identified in 20% of patients with angiosarcoma. Outcomes of matched targeted therapy of patients with actionable targets will be presented with more mature follow-up. Conclusions: Targeted NGS of DNA from archival FFPE tissue is feasible with the potential for identifying actionable targets and discovery of novel mutations.

scholarly journals Clinical Application of Next-Generation Sequencing of Plasma Cell-Free DNA for Genotyping Untreated Advanced Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2707
Author(s):  
Maria Gabriela O. Fernandes ◽  
Natália Cruz-Martins ◽  
Conceição Souto Moura ◽  
Susana Guimarães ◽  
Joana Pereira Reis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Clinical Outcomes ◽  
Test Performance ◽  
Molecular Diagnostic ◽  
Test Accuracy ◽  
Newly Diagnosed ◽  
Next Generation ◽  
Clinical Value ◽  
Generation Sequencing

Background: Analysis of circulating tumor DNA (ctDNA) has remarkable potential as a non-invasive lung cancer molecular diagnostic method. This prospective study addressed the clinical value of a targeted-gene amplicon-based plasma next-generation sequencing (NGS) assay to detect actionable mutations in ctDNA in patients with newly diagnosed advanced lung adenocarcinoma. Methods: ctDNA test performance and concordance with tissue NGS were determined, and the correlation between ctDNA findings, clinical features, and clinical outcomes was evaluated in 115 patients with paired plasma and tissue samples. Results: Targeted-gene NGS-based ctDNA and NGS-based tissue analysis detected 54 and 63 genomic alterations, respectively; 11 patients presented co-mutations, totalizing 66 hotspot mutations detected, 51 on both tissue and plasma, 12 exclusively on tissue, and 3 exclusively on plasma. NGS-based ctDNA revealed a diagnostic performance with 81.0% sensitivity, 95.3% specificity, 94.4% PPV, 83.6% NPV, test accuracy of 88.2%, and Cohen’s Kappa 0.764. PFS and OS assessed by both assays did not significantly differ. Detection of ctDNA alterations was statistically associated with metastatic disease (p = 0.013), extra-thoracic metastasis (p = 0.004) and the number of organs involved (p = 0.010). Conclusions: This study highlights the potential use of ctDNA for mutation detection in newly diagnosed NSCLC patients due to its high accuracy and correlation with clinical outcomes.

scholarly journals Precision Oncology in Sarcomas: Divide and Conquer

2019 ◽  
pp. 1-16 ◽  
Author(s):  
Roberto Carmagnani Pestana ◽  
Roman Groisberg ◽  
Jason Roszik ◽  
Vivek Subbiah
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue Sarcomas ◽  
Genetic Alterations ◽  
Divide And Conquer ◽  
Precision Oncology ◽  
Next Generation ◽  
Mesenchymal Tumors ◽  
Next Generation Sequencing Technology ◽  
Molecular Abnormalities ◽  
Generation Sequencing

Sarcomas are a heterogeneous group of rare malignancies that exhibit remarkable heterogeneity, with more than 50 subtypes recognized. Advances in next-generation sequencing technology have resulted in the discovery of genetic events in these mesenchymal tumors, which in addition to enhancing understanding of the biology, have opened up avenues for molecularly targeted therapy and immunotherapy. This review focuses on how incorporation of next-generation sequencing has affected drug development in sarcomas and strategies for optimizing precision oncology for these rare cancers. In a significant percentage of soft tissue sarcomas, which represent up to 40% of all sarcomas, specific driver molecular abnormalities have been identified. The challenge to evaluate these mutations across rare cancer subtypes requires the careful characterization of these genetic alterations to further define compelling drivers with therapeutic implications. Novel models of clinical trial design also are needed. This shift would entail sustained efforts by the sarcoma community to move from one-size-fits-all trials, in which all sarcomas are treated similarly, to divide-and-conquer subtype-specific strategies.

scholarly journals Next-Generation Sequencing in Acute Lymphoblastic Leukemia

2019 ◽  
Vol 20 (12) ◽  
pp. 2929 ◽  
Author(s):  
Nicoletta Coccaro ◽  
Luisa Anelli ◽  
Antonella Zagaria ◽  
Giorgina Specchia ◽  
Francesco Albano
Keyword(s):  
Next Generation Sequencing ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Age Of Onset ◽  
Lymphoblastic Leukemia ◽  
Genomic Analysis ◽  
Next Generation ◽  
Acute Leukemias ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and accounts for about a quarter of adult acute leukemias, and features different outcomes depending on the age of onset. Improvements in ALL genomic analysis achieved thanks to the implementation of next-generation sequencing (NGS) have led to the recent discovery of several novel molecular entities and to a deeper understanding of the existing ones. The purpose of our review is to report the most recent discoveries obtained by NGS studies for ALL diagnosis, risk stratification, and treatment planning. We also report the first efforts at NGS use for minimal residual disease (MRD) assessment, and early studies on the application of third generation sequencing in cancer research. Lastly, we consider the need for the integration of NGS analyses in clinical practice for genomic patients profiling from the personalized medicine perspective.

scholarly journals Final report of ENGAGE ‐ Establishing Next Generation sequencing Ability for Genomic analysis in Europe

2018 ◽  
Vol 15 (6) ◽  
Author(s):  
Rene S. Hendriksen ◽  
Susanne Karlsmose Pedersen ◽  
Pimlapas Leekitcharoenphon ◽  
Burkhard Malorny ◽  
Maria Borowiak ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genomic Analysis ◽  
Final Report ◽  
Next Generation ◽  
Generation Sequencing

Next-generation sequencing yields promising targets in advanced cholangiocarcinoma (CCA).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 209-209
Author(s):  
Rachna T. Shroff ◽  
Chaitanya Churi ◽  
Asif Rashid ◽  
Lopa Mishra ◽  
Mingxin Zuo ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Kras Mutation ◽  
Cancer Center ◽  
Next Generation ◽  
Illumina Hiseq ◽  
Md Anderson ◽  
Genetic Profiles ◽  
Next Generation Sequencing Ngs ◽  
Parp 1 ◽  
Generation Sequencing

209 Background: The incidence of CCA is rising and the clinical efficacy of systemic therapy is suboptimal. Next generation sequencing (NGS) technology offers potential for targeted therapeutics against genetically heterogenous solid tumors including cholangiocarcinoma (CCA). Methods: DNA was extracted from biopsy specimens of 61 patients (pts) with CCA seen at MD Anderson Cancer Center Houston, TX. DNA sequencing was performed for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes to an average depth of 1000X using the Illumina HiSeq 2000 platform (performed by Foundation Medicine, Cambridge, MA). Results: 174genomic alterations (GA) were identified from 61 pt samples with an average of 2.85 GAs/pt (range 0-10). GAs identified were mutations (75%), amplifications (16%), loss/deletions (7%) and others (2%). 6 (10%) tumors showed no GAs. Most frequent GAs were TP53 (34%), KRAS (30%), ARID1A (15%), PBRM1 (11%), BAP1 (8%), ERBB2 (8%), FBXW7 (8%), SMAD4 (8%) and IDH1 (8%). ERBB2 GAs included 4 mutations and 1 amplification. KRAS mutation was associated with a statistically significant reduction in overall survival (OS). Mean OS in pts with KRAS mutation was 32 weeks vs. 63 weeks in KRAS wt (t = -2.126, p = 0.039). Ingenuity Pathway Analysis indicated disruption in cell cycle, proliferation, development, death and DNA repair pathways. Targetable signaling pathways from this study are described in the Table. Targetable GAs were noted in 62% of pts. These are potentially targetable by inhibitors to ERBB2, FGF, mTOR, MEK, BRAF and PARP-1. Conclusions: These data are the single largest compilation of NGS analysis on CCA pts and demonstrate the range of GAs that are eligible for investigational targeted therapies. These results can be used as a basis to develop personalized treatments for CCA pts based on individual genetic profiles. [Table: see text]

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