Abstract 5354: Evaluation of quantity, quality and performance with the TruSight® Tumor 170 solid tumor profiling assay of nucleic acids extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections

LoCoco, Jennifer S.; Li, Teng; Chou, Danny Hung‐Chieh; Chang, Xiao; Luo, Byron; Sayne, Jennifer; Adams, Ashley; Ajili, Naseem; Chivers, Cody; Murthy, Beena; Ball, Laurel; Castaneda, Allan; Clark, Katie; Crain, Brian; Daulo, Anthony; Do, Manh; Du, Tingting; Dumm, Sarah; Han, Yonmee; Havern, Michael; Hsieh, Chia‐Ling; Jiang, Tingting; Johansen, Suzanne; Lang, Scott; Liang, Ruyi; McLean, Jaime; Nassiri, Yousef; Purdy, Austin; Rostron, Jason; Silhavy, Jennifer L.; June, Snedecor; Talago, Natasha; Wu, Kevin; Zhao, Chen; Zlatkov, Clare; Kuraishy, Ali; Gutekunst, Karen; Rozieres, Sohela de; Friedenberg, Matthew C.; Chuang, Han‐Yu; Jäger, Anne Charlotte

doi:10.1158/1538-7445.am2017-5354

Cited by 2 publications

(2 citation statements)

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“…The TST170 uses a hybrid-capture method to extract DNA and RNA to detect SNVs, indels, selected rearrangements, and fusions. 19,20 Herein we report pathogenic changes that occurred in 14 genes involved in DDR…”

Section: Stagementioning

confidence: 97%

Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

Gilson

Ingleby

Gilbert

et al. 2020

JCO Precision Oncology

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PURPOSE The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor ( AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences ( AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

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Section: Stagementioning

confidence: 97%

Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

Gilson

Ingleby

Gilbert

et al. 2020

JCO Precision Oncology

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“…Tumour tissue resected at surgery will undergo testing at a single study reference laboratory using the Illumina TruSight 170 molecular screening panel, capable of detecting the somatic mutation profile of 170 genes, SNV, indel (151 genes), copy number abnormalities (59 genes) and gene fusion and splice variants (55 genes). [18][19][20] The planned duration of recruitment for the study was between 1 May 2020 and 31 May 2021.…”

Section: Study Plan Molecular Phenotyping To Generate Molecular Pathology Reportmentioning

confidence: 99%

LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study

et al. 2021

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IntroductionGrades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsiesMethods and analysisThis study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library preparation and targeted capture will be performed using the TruSight Tumor 170 (TST170) kit and samples sequenced on NextSeq 550 (Illumina) using NextSeq V.2.5 hi output reagents, according to the manufacturer’s instructions. Data analysis will be performed using the Illumina BaseSpace TST170 app v1.02 and a custom tertiary pipeline, implemented within the Clinical Genomics Workspace software platform from PierianDx (also refer to section 3.2). Primary outcomes for the study will be the number of patients enrolled and the number of patients who complete molecular screening. Secondary outcomes will include the proportion of screened patients enrolled; proportion of patients who complete molecular screening; the turn-around time of molecular screening; and the value of a brain tumour specific multi-disciplinary tumour board, called the molecular tumour advisory panel as measured by the proportion of patients in whom the treatment recommendation was refined compared with the recommendations from the automated bioinformatics platform of the reference laboratory testing.Ethics and disseminationThe study was approved by the lead Human Research Ethics Committee of the Sydney Local Health District: Protocol No. X19-0383. The study will be conducted in accordance with the principles of the Declaration of Helsinki 2013, guidelines for Good Clinical Practice and the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2007, updated 2018 and as amended periodically). Results will be disseminated using a range of media channels including newsletters, social media, scientific conferences and peer-reviewed publications.Trial registration numberACTRN12620000087954; Pre-results.

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Abstract 5354: Evaluation of quantity, quality and performance with the TruSight® Tumor 170 solid tumor profiling assay of nucleic acids extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections

Cited by 2 publications

References 0 publications

Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial

LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study

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