The impact of whole genome and transcriptome analysis (WGTA) on predictive biomarker discovery and diagnostic accuracy of advanced malignancies

The Journal of Pathology: Clinical Research

Andrew J Mungall¹  Martin R Jones¹  Karen Mungall¹  Erin Pleasance¹  Laura Williamson¹  Yaoqing Shen¹  Marco A Marra¹  Steven JM Jones¹  Jasleen K Grewal¹  Dean A Regier²  Diana Ionescu³  David G Huntsman⁴  Cheng Han Lee⁴  Chris Dunham⁵  Anthony N Karnezis⁶  Anna F Lee⁷  Ellen Cai⁷  Stephen Yip⁷  Ellia Zhong⁷  Julia R Naso⁷  Basile Tessier‐Cloutier⁷  C Blake Gilks⁸  Tony Ng⁸  Brian Skinnider⁸  Lynn Hoang⁸  Basil Horst⁸  David F Schaeffer⁸  Tyler Smith⁸  Brandon S Sheffield⁹  Janessa Laskin^1,10  David DW Twa^1,11  Tae Hoon Lee^1,11 

[1] Canada's Michael Smith Genome Sciences Centre Vancouver BC Canada;Cancer Control Research BC Cancer Vancouver BC Canada;Department of Anatomical Pathology BC Cancer Vancouver BC Canada;Department of Molecular Oncology BC Cancer Vancouver BC Canada;Department of Pathology and Laboratory Medicine Children's and Women's Health Centre of British Columbia Vancouver BC Canada;Department of Pathology and Laboratory Medicine UC Davis Sacramento CA USA;Department of Pathology and Laboratory Medicine University of British Columbia Vancouver BC Canada;Department of Pathology and Laboratory Medicine Vancouver General Hospital Vancouver BC Canada;Department of Pathology and Laboratory Medicine William Osler Health System Brampton ON Canada;Division of Medical Oncology BC Cancer Vancouver BC Canada;Faculty of Medicine University of British Columbia Vancouver BC Canada;

关键词: biomarker;    diagnostic;    WGTA;    pathology;    precision medicine;    oncology;   

DOI  :  10.1002/cjp2.265

来源: DOAJ

【 摘 要 】

Abstract In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non‐MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non‐contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.

【 授权许可】

Unknown