scholarly journals Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy

2016 ◽  
pp. now254 ◽  
Author(s):  
Cassie N. Kline ◽  
Nancy M. Joseph ◽  
James P. Grenert ◽  
Jessica van Ziffle ◽  
Eric Talevich ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Germline Mutations ◽  
Next Generation ◽  
Oncology Patients ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

scholarly journals The Genetic Germline Background of Single and Multiple Primary Melanomas

2021 ◽  
Vol 7 ◽  
Author(s):  
Simona De Summa ◽  
Antonia Lasorella ◽  
Sabino Strippoli ◽  
Giuseppe Giudice ◽  
Gabriella Guida ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cell Cycle Control ◽  
Germline Mutations ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Multiple Genes ◽  
Multiple Primary ◽  
Small Cohort ◽  
Sequencing Platforms ◽  
Generation Sequencing

Background:Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel.Materials and Methods:A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence.Results:We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs,p= 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p= 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development.Conclusions:In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.

scholarly journals Rare Germline Mutations Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma

2014 ◽  
Vol 99 (7) ◽  
pp. E1352-E1360 ◽  
Author(s):  
Jenny Welander ◽  
Adam Andreasson ◽  
C. Christofer Juhlin ◽  
Roger W. Wiseman ◽  
Martin Bäckdahl ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Germline Mutations ◽  
Susceptibility Genes ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Pilot study of clinical targeted next generation sequencing for prostate cancer: Consequences for treatment and genetic counseling.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 251-251
Author(s):  
Heather H. Cheng ◽  
Nola Klemfuss ◽  
Robert B. Montgomery ◽  
Celestia S. Higano ◽  
Michael Thomas Schweizer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Next Generation Sequencing ◽  
Pilot Study ◽  
Germline Mutations ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Targeted Ngs ◽  
High Penetrance ◽  
Generation Sequencing

251 Background: Targeted next generation sequencing (NGS) panels for identification of actionable mutations are increasingly used in oncology for therapeutic decision-making, but have yet to be widely used for prostate cancer.To determine the utility of applying a targeted next generation sequencing to prostate cancer management, we conducted a pilot study using the clinical molecular diagnostic assay, UW-OncoPlex, on primary and metastatic tumors from patients with prostate cancer. Methods: Patients receiving treatment for prostate cancer by a medical oncologist were eligible. After providing informed consent, tumor DNA was extracted from formalin-fixed, paraffin-embedded (FFPE)primary tumors and/or metastatic biopsies. Extracted DNA was analyzed using UW-OncoPlex, a targeted NGS panel designed to assess genomic alterations in 234 cancer-associated genes (PMID: 24189654). Results were discussed at a monthly multidisciplinary precision tumor board prior to communicating results to patients. Results: Forty patients consented to the study and 31 (78%) had reportable results. Findings included frequently observed prostate cancer genomic aberrations, including: TMPRSS2-ERG fusions and copy-number alterations of PTEN, TP53, FOXA1, AR, and SPOP. We also observed potentially actionable alterations in BRAF, MAP2K1 (MEK1), PIK3R1, MET, FGFR1, and FGFR3, which inform future treatment and clinical trial considerations. Notably, 8/31 (25%) patients had suspected high penetrance germline mutations, including in BRCA2 (N = 3), TP53 (N = 2), ATM (N = 1), and CHEK2 (N = 2). These 8 individuals were referred to medical genetics and 7 of 8 mutations were confirmed to be germline. One patient was found to have a hypermutated phenotype associated with bi-allelic MSH6 mutation and microsatellite instability. Conclusions: Targeted NGS panel testing may be useful in informing future treatment approaches and clinical trial selection for patients with prostate cancer. In addition, we observed a high proportion of cases with suspected high-penetrance germline mutations and immediate actionability through referral to medical genetics.

Mutational landscape by targeted next-generation sequencing in EBV-associated lymphoepithelioma-like cholangiocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 269-269
Author(s):  
Nai-Jung Chiang ◽  
Ming-Huang Chen ◽  
Li-Tzong Chen ◽  
Shan Yanshen
Keyword(s):  
Next Generation Sequencing ◽  
Peripheral Blood ◽  
Copy Number ◽  
Somatic Mutations ◽  
Tumor Tissue ◽  
Germline Mutations ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing ◽  
Cancer Panel

269 Background: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of intrahepatic cholangiocarcinoma, which is highly associated with EBV infection and abundant lymphoplasmacytic cell infiltration. However, there’s limited data of genetic background in LELCC. Therefore, we want to explore the mutation profiles of LELCC, as well as copy number variations. Methods: Five patients’ tumor tissues diagnosed as LELCC, with positive EBER expression were retrospectively collected and microscopically dissected. Of them, two patients’ peripheral blood mononuclear cell served as background of germline mutations. Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes for analysis of tumor tissue and blood. PDL1 immunohistochemistry staining with 22C3 antibody pharmDx was applied. Results: All EBV-associated LELCC showed positive expression of PDL1 staining, with combined positive score from 5% to 30%. Both somatic and germline mutations can be detected in LELCC tissue because diffuse infiltration of lymphocytes over tumor. After adjusting for background germline mutation frequency from peripheral blood, only mutations with allele frequency less than or around 10% were considered as somatic mutations. Overall, 10 nonsynonymous somatic mutations were detected in 4 (80%) patients with a range of 1-5 mutations per sample. Mutations were identified including BARD1, EPHA5, MUC16, TNFAIP3, CD19, PTEN, TET1, RECQL4, CD79B, and KDM5A. Copy number changes were rare in this special population. Interesting, one patient who failed to gemcitabine plus cisplatin got partial response after anti-PD1 inhibitor treatment. Conclusions: LELCC is highly correlated with PDL1 expression in tumor and immune cells. It’s necessary to have both tumor tissue and peripheral blood for next-generation sequencing to identify truly somatic mutations in LELCC.

scholarly journals Targeted next-generation sequencing of 565 neuro-oncology patients at UCLA: A single-institution experience

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Matthew S Ji ◽  
Blaine S C Eldred ◽  
Regina Liu ◽  
Sean T Pianka ◽  
Donna Molaie ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Next Generation Sequencing ◽  
Diagnostic Markers ◽  
Cns Tumors ◽  
Next Generation ◽  
Oncology Patients ◽  
Targeted Next Generation Sequencing ◽  
Targeted Ngs ◽  
Unknown Significance ◽  
Generation Sequencing

Abstract Background Targeted next-generation sequencing (NGS) is frequently obtained at the University of California, Los Angeles (UCLA) for clinical characterization of CNS tumors. In this study, we describe the diagnostic reliability of the Foundation Medicine (FM) targeted NGS platform and its ability to explore and identify tumor characteristics of prognostic significance in gliomas. Methods Neuro-oncology patients seen at UCLA who have received FM testing between August 2012 and March 2019 were included in this study, and all mutations from FM test reports were recorded. Initial tumor diagnoses and diagnostic markers found via standard clinical methods were obtained from pathology reports. With overall and progression-free survival data, elastic net regularized Cox regression and Cox proportional hazards models were used to determine whether any mutations of unknown significance detected by FM could predict patient outcome in glioblastoma (GBM). Results Six hundred and three samples tested by FM from 565 distinct patients were identified. Concordance of diagnostic markers was high between standard clinical testing methods and FM. Oligodendroglial markers detected via FM were highly correlated with 1p19q codeletion in IDH mutated gliomas. FM testing of multiple tumor samples from the same patient demonstrated temporal and spatial mutational heterogeneity. Mutations in BCORL1, ERBB4, and PALB2, which are mutations of unknown significance in GBM, were shown to be statistically significant in predicting patient outcome. Conclusions In our large cohort, we found that targeted NGS can both reliably and efficiently detect important diagnostic markers in CNS tumors.

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