A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary.

2023-01-01

Posner, Atara

Prall, Owen Wj

Sivakumaran, Tharani

Etemadamoghadam, Dariush

Thio, Niko

Pattison, Andrew

Balachander, Shiva

Fisher, Krista

Webb, Samantha

Wood, Colin

DeFazio, Anna

Wilcken, Nicholas

Gao, Bo

Karapetis, Christos S

Singh, Madhu

Collins, Ian M

Richardson, Gary

Steer, Christopher

Warren, Mark

Karanth, Narayan

Wright, Gavin

Williams, Scott

George, Joshy

Hicks, Rodney J

Boussioutas, Alex

Gill, Anthony J

Solomon, Benjamin J

Xu, Huiling

Fellowes, Andrew

Fox, Stephen B

Schofield, Penelope

Bowtell, David

Mileshkin, Linda

Tothill, Richard W

Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.

Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.

Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

The Westmead Institute for Medical Research, Sydney, NSW, Australia.

Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.

The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia.

Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia.

Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia.

Department of Medical Oncology, Flinders University and Flinders Medical Centre, Adelaide, SA, Australia.

Department of Medical Oncology, Barwon Health Cancer Services, Geelong, VIC, Australia.

Department of Medical Oncology, SouthWest HealthCare, Warrnambool and Deakin University, Geelong, VIC, Australia.

Department of Medical Oncology, Cabrini Health, Melbourne, VIC, Australia.

Border Medical Oncology, Albury Wodonga Regional Cancer Centre, Albury, NSW, Australia.

Department of Medical Oncology, Bendigo Health, Bendigo, VIC, Australia.

Division of Medicine, Alan Walker Cancer Centre, Darwin, NT, Australia.

Department of Cardiothoracic Surgery, St Vincent's Hospital, Melbourne, VIC, Australia.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Computational Sciences, The Jackson Laboratory, Farmington, Connecticut, USA.

The St Vincent's Hospital Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.

Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.

Cancer Diagnosis and Pathology Group, Kolling Institute of Medical, Research and Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Department of Psychology, and Iverson Health Innovation Research Institute, Swinburne University, Melbourne, VIC, Australia.

Behavioural Sciences Unit, Health Services Research and Implementation Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

cancer diagnostic

cancer of unknown primary

gene expression profiling

mutation profiling

targeted therapy

tissue of origin classification

Humans

Neoplasms, Unknown Primary

Prospective Studies

Retrospective Studies

Australia

Gene Expression Profiling

Sequence Analysis, DNA

RNA

Journal Article

Publication

0000-0002-1592-6127

0000-0003-4522-1184

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high-medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs - 80% had high-medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high-medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

link

J Pathol . 2023 Jan;259(1):81-92. doi: 10.1002/path.6022. Epub 2022 Nov 30.

1096-9896

https://pubmed.ncbi.nlm.nih.gov/36287571/?otool=iaurydwlib