Characterization of advanced hepatocellular carcinoma patients via a multi-omic cancer registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16617-e16617
Author(s):  
Joseph S Ryan ◽  
Xiaojun Xu ◽  
Pablo Tamayo ◽  
Adam Burgoyne
Keyword(s):  
Hepatocellular Carcinoma ◽  
Next Generation Sequencing ◽  
Cancer Registry ◽  
Tumor Tissue ◽  
Response To Therapy ◽  
Variant Allele ◽  
Advanced Hepatocellular Carcinoma ◽  
Next Generation ◽  
Tumor Tissues ◽  
Generation Sequencing

e16617 Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and has significant cancer-related mortality worldwide. Molecularly matched therapy has an emerging role in HCC treatment; however, HCC poses a unique challenge as patients are frequently diagnosed radiographically rather than by tissue biopsy, limiting our ability to utilize tumor tissue data for therapy selection. The purpose of this study is to establish a multi-omic database with matched demographic and clinical data to identify patterns of shared molecular aberrations in HCC tumors. Methods: An institutional HCC cancer registry was created, and a retrospective review was performed using data from 2017-2020 at a tertiary cancer center. 56 patients with advanced HCC were identified, and tissue samples were analyzed with multi-omic profiling assays (next generation DNA sequencing, RNA sequencing, protein expression via immunohistochemistry) versus ctDNA from peripheral blood. Results: Next generation sequencing was obtained for 38 (76%) patients using either tissue or ctDNA. While the results were similar, a higher number of total mutations were identified using tumor tissues rather than ctDNA. The average variant allele fraction for tumor tissues was approximately 10x higher than the variant allele fractions identified by ctDNA. However, ctDNA sequencing identified a higher number of potentially actionable mutations, on average, than did tissue testing. The most commonly mutated genes included TERT (42% of patients), TP53 (47%), CTNNB1 (34%), ARID1A (18%), CCND1 (16%), and NEF2L2 (13%). Several patients had serial ctDNA sequencing, which showed an increase in actionable and total mutations over time as well as changes in variant allele fractions in response to therapy. Conclusions: Next generation sequencing of ctDNA can be used in lieu of tumor tissue in patients diagnosed with HCC radiographically to identify actionable mutations, but it may underestimate the mutational burden of HCC tumors. Serial analyses with cell free DNA may be useful to monitor clonal evolution in response to targeted treatment and may identify new actionable mutations as patients progress on systemic therapies. [Table: see text]

scholarly journals Next‐Generation Sequencing of Circulating Tumor DNA Reveals Frequent Alterations in Advanced Hepatocellular Carcinoma

2018 ◽  
Vol 23 (5) ◽  
pp. 586-593 ◽  
Author(s):  
Sadakatsu Ikeda ◽  
Igor F. Tsigelny ◽  
Åge A. Skjevik ◽  
Yuko Kono ◽  
Michel Mendler ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Next Generation Sequencing ◽  
Circulating Tumor Dna ◽  
Advanced Hepatocellular Carcinoma ◽  
Next Generation ◽  
Tumor Dna ◽  
Generation Sequencing

scholarly journals EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i51-i51
Author(s):  
Alexandra Miller ◽  
Luca Szalontay ◽  
Nancy Bouvier ◽  
Hamza Ahmed ◽  
Katherine Hill ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Next Generation Sequencing ◽  
Young Adult ◽  
Molecular Diagnostics ◽  
Tumor Tissue ◽  
Response To Therapy ◽  
Adolescent And Young Adult ◽  
Low Grade ◽  
Next Generation ◽  
Generation Sequencing

Abstract Purpose Pediatric central nervous system tumors remain a leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be challenging. Subclinical detection of disease prior to clinical or imaging progression may provide opportunity for earlier intervention and ultimately improve overall survival. Additionally, our understanding of molecular evolution in response to therapy remains limited, given the rarity of serial sampling of tumor tissue. Methods We report our experience with minimally invasive molecular diagnostics using a validated next generation sequencing assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) obtained at the time of surgery, by intraventricular catheter or lumbar puncture. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. Results We analyzed 64 CSF samples from 45 pediatric and adolescent and young adult (AYA) patients (pediatric=25; AYA=20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n=10), medulloblastoma (n=10), pineoblastoma (n=5), low grade glioma (n=4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n=4), metastatic retinoblastoma (n=4), ependymoma (n=3), and other (n=5). Somatic alterations were detected in 28/64 samples (44.4%) and in at least one sample per unique patient in 22/45 patients (48.8%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (86.3%). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course. Conclusion We identified four general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: 1) diagnosis; 2) identification of actionable alterations; 3) track response to therapy; and 4) monitoring tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population that may improve care.

A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next- Generation Sequencing

2020 ◽  
Vol 15 ◽  
Author(s):  
Zheng Jiang ◽  
Hui Liu ◽  
Siwen Zhang ◽  
Jia Liu ◽  
Weitao Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Microsatellite Instability ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
High Sensitivity ◽  
Next Generation ◽  
Tissue Samples ◽  
Next Generation Sequencing Technology ◽  
Medication Selection ◽  
Generation Sequencing

Background: Microsatellite instability (MSI) is a prognostic biomarker used to guide medication selection in multiple cancers, such as colorectal cancer. Traditional PCR with capillary electrophoresis and next-generation sequencing using paired tumor tissue and leukocyte samples are the main approaches for MSI detection due to their high sensitivity and specificity. Currently, patient tissue samples are obtained through puncture or surgery, which causes injury and risk of concurrent disease, further illustrating the need for MSI detection by liquid biopsy. Methods: We propose an analytic method using paired plasma/leukocyte samples and MSI detection using next-generation sequencing technology. Based on the theoretical progress of oncogenesis, we hypothesized that the microsatellite site length in plasma equals the combination of the distribution of tumor tissue and leukocytes. Thus, we defined a window-judgement method to identify whether biomarkers were stable. Results: Compared to traditional PCR as the standard, we evaluated three methods in 20 samples (MSI-H:3/MSS:17): peak shifting method using tissue vs. leukocytes, peak shifting method using plasma vs. leukocytes, and our method using plasma vs. leukocytes. Compared to traditional PCR, we observed a sensitivity of 100%, 0%, and 100%, and a specificity of 100.00%, 94.12%, and 88.24%, respectively. Conclusion: Our method has the advantage of possibly detecting MSI in a liquid biopsy and provides a novel direction for future studies to increase the specificity of the method.

scholarly journals Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Somatic Mutations in CDH1 and Other Clinically Actionable Mutations Imply Early Use of Targeted Agents

2021 ◽  
Vol 28 (1) ◽  
pp. 918-927
Author(s):  
Lei-Chi Wang ◽  
Tai-Chi Lin ◽  
Yi-Chen Yeh ◽  
Hsiang-Ling Ho ◽  
Chieh-Chih Tsai ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cell Carcinoma ◽  
Tumor Tissue ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Next Generation ◽  
Signet Ring ◽  
Ring Cell ◽  
Generation Sequencing ◽  
E Cadherin

Primary signet ring cell/histiocytoid carcinoma of the eyelid is a rare ocular malignancy and its diagnosis is often delayed. This neoplasm presents as an insidious, diffusely infiltrative mass in the periocular area that later infiltrates the orbit. An exenteration is usually indicated; however, nearly one-third of patients develop local recurrence or metastasis. Morphologically, it resembles signet ring cell carcinoma of the stomach and breast, raising the possibility of mutations in CDH1, the gene encoding E-cadherin. To determine whether primary signet ring cell/histiocytoid carcinoma harbors the CDH1 mutation or other actionable mutations, we analyzed the tumor tissue via next-generation sequencing. We identified only one case of primary signet ring cell carcinoma of the eyelid with adequate DNA quality for sequencing from the pathological archive during the period 2000 to 2020. A comprehensive evaluation including histopathology, immunohistochemistry, and next-generation sequencing assay was performed on tumor tissue. Immunohistochemically, the tumor exhibited E-cadherin membranous staining with the aberrant cytoplasmic staining of β-catenin. Using next-generation sequencing, we demonstrated the mutation in the CDH1 gene. In addition, other clinically actionable mutations including ERBB2 and PIK3CA were also detected. The alterations in other actionable genes indicate a need for larger studies to evaluate the pathogenesis and potential therapies for primary signet ring cell/histiocytoid carcinoma of the eyelid.

A novel B*07 variant allele, B*07:416 , identified by next‐generation sequencing

HLA ◽  
2021 ◽  
Author(s):  
Mei San Tang ◽  
Brian F. Duffy ◽  
Jo‐Ellen Jennemann ◽  
Bijal A. Parikh ◽  
Chang Liu
Keyword(s):  
Next Generation Sequencing ◽  
Variant Allele ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Lavage of the Uterine Cavity for Molecular Detection of Müllerian Duct Carcinomas: A Proof-of-Concept Study

2015 ◽  
Vol 33 (36) ◽  
pp. 4293-4300 ◽  
Author(s):  
Elisabeth Maritschnegg ◽  
Yuxuan Wang ◽  
Nina Pecha ◽  
Reinhard Horvat ◽  
Els Van Nieuwenhuysen ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Tissue ◽  
Massively Parallel Sequencing ◽  
Uterine Cavity ◽  
Mullerian Duct ◽  
Next Generation ◽  
Benign Lesions ◽  
Cavity Detection ◽  
Müllerian Duct ◽  
Generation Sequencing

Purpose Type II ovarian cancer (OC) and endometrial cancer (EC) are generally diagnosed at an advanced stage, translating into a poor survival rate. There is increasing evidence that Müllerian duct cancers may exfoliate cells. We have established an approach for lavage of the uterine cavity to detect shed cancer cells. Patients and Methods Lavage of the uterine cavity was used to obtain samples from 65 patients, including 30 with OC, five with EC, three with other malignancies, and 27 with benign lesions involving gynecologic organs. These samples, as well as corresponding tumor tissue, were examined for the presence of somatic mutations using massively parallel sequencing (next-generation sequencing) and, in a subset, singleplex analysis. Results The lavage technique could be applied successfully, and sufficient amounts of DNA were obtained in all patients. Mutations, mainly in TP53, were identified in 18 (60%) of 30 lavage samples of patients with OC using next-generation sequencing. Singleplex analysis of mutations previously determined in corresponding tumor tissue led to further identification of six patients. Taken together, in 24 (80%) of 30 patients with OC, specific mutations could be identified. This also included one patient with occult OC. All five analyzed lavage specimens from patients with EC harbored mutations. Eight (29.6%) of 27 patients with benign lesions tested positive for mutations, six (75%) as a result of mutations in the KRAS gene. Conclusion This study proved that tumor cells from ovarian neoplasms are shed and can be collected via lavage of the uterine cavity. Detection of OC and EC and even clinically occult OC was achieved, making it a potential tool of significant promise for early diagnosis.

scholarly journals Profiling DNA Methylation Based on Next-Generation Sequencing Approaches: New Insights and Clinical Applications

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Daniela Barros-Silva ◽  
C. Marques ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Dna Methylation ◽  
Next Generation Sequencing ◽  
High Throughput Sequencing ◽  
Epigenetic Modification ◽  
Response To Therapy ◽  
Next Generation ◽  
Sequencing Technologies ◽  
Prognosis And Prediction ◽  
Novel Biomarkers ◽  
Generation Sequencing

DNA methylation is an epigenetic modification that plays a pivotal role in regulating gene expression and, consequently, influences a wide variety of biological processes and diseases. The advances in next-generation sequencing technologies allow for genome-wide profiling of methyl marks both at a single-nucleotide and at a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, coverage, and bioinformatics analysis. Thus, the selection of the most feasible method according with the project’s purpose requires in-depth knowledge of those techniques. Currently, high-throughput sequencing techniques are intensively used in epigenomics profiling, which ultimately aims to find novel biomarkers for detection, diagnosis prognosis, and prediction of response to therapy, as well as to discover new targets for personalized treatments. Here, we present, in brief, a portrayal of next-generation sequencing methodologies’ evolution for profiling DNA methylation, highlighting its potential for translational medicine and presenting significant findings in several diseases.

scholarly journals Genomic heterogeneity: next-generation sequencing enables biomarker identification for hepatocellular carcinoma

2017 ◽  
Vol 11 (7) ◽  
pp. 515-518 ◽  
Author(s):  
Demosthenes E Ziogas ◽  
Efstathios G Lykoudis ◽  
Dimitrios H Roukos ◽  
Georgios K Glantzounis
Keyword(s):  
Hepatocellular Carcinoma ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Biomarker Identification ◽  
Generation Sequencing
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