Review

. 2025 Aug;14(15):e71080.

doi: 10.1002/cam4.71080.

Utility of Germline, Somatic and ctDNA Testing in Adults With Cancer

Emily DeBortoli¹, Ella McGahan¹, Tatiane Yanes¹, Jennifer Berkman¹, Lauren G Aoude², Amelia K Smit^{3

4}, Akira Gokoolparsadh⁵, Azure Hermes⁶, Lyndsay Newett⁶, Mackenzie Bourke⁷, Susan Hanson⁸, Helen Hughes⁸, Oliver Hofmann⁹, Ilias Goranitis^{7

10}, Rebekah McWhirter¹¹, Vivienne Milch^{8

12}, Julia Steinberg³, Aideen McInerney-Leo¹

Affiliations

¹ Dermatology Research Centre, The Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia.
² Frazer Institute, The University of Queensland, Brisbane, QLD, Australia.
³ The Daffodil Centre, The University of Sydney, a Joint Venture With Cancer Council New South Wales, Sydney, New South Wales, Australia.
⁴ Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
⁵ Faculty of Medicine and Health, Sydney School of Public Health, Sydney Health Ethics, The University of Sydney, Sydney, New South Wales, Australia.
⁶ National Centre for Indigenous Genomics, Australian National University, Canberra, Australia Capital Territory, Australia.
⁷ Economics of Genomics and Precision Medicine Unit, Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Cancer Australia, Sydney, New South Wales, Australia.
⁹ University of Melbourne Centre for Cancer Research, Melbourne, Victoria, Australia.
¹⁰ Australian Genomics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹¹ School of Law, Australian National University, Canberra, Australia.
¹² Caring Futures Institute, Flinders University, Adelaide, South Australia, Australia.

PMID: 40747594
PMCID: PMC12314551
DOI: 10.1002/cam4.71080

Review

Utility of Germline, Somatic and ctDNA Testing in Adults With Cancer

Emily DeBortoli et al. Cancer Med. 2025 Aug.

. 2025 Aug;14(15):e71080.

doi: 10.1002/cam4.71080.

Authors

Affiliations

¹ Dermatology Research Centre, The Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia.
² Frazer Institute, The University of Queensland, Brisbane, QLD, Australia.
³ The Daffodil Centre, The University of Sydney, a Joint Venture With Cancer Council New South Wales, Sydney, New South Wales, Australia.
⁴ Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
⁵ Faculty of Medicine and Health, Sydney School of Public Health, Sydney Health Ethics, The University of Sydney, Sydney, New South Wales, Australia.
⁶ National Centre for Indigenous Genomics, Australian National University, Canberra, Australia Capital Territory, Australia.
⁷ Economics of Genomics and Precision Medicine Unit, Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Cancer Australia, Sydney, New South Wales, Australia.
⁹ University of Melbourne Centre for Cancer Research, Melbourne, Victoria, Australia.
¹⁰ Australian Genomics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹¹ School of Law, Australian National University, Canberra, Australia.
¹² Caring Futures Institute, Flinders University, Adelaide, South Australia, Australia.

PMID: 40747594
PMCID: PMC12314551
DOI: 10.1002/cam4.71080

Abstract

Background and aim: Historical genetic sequencing of specific cancer variants has been superseded by comprehensive genomic profiling (CGP). This narrative review aimed to capture current international evidence on the clinical utility of CGP for cancer prevention, detection and treatment.

Materials and methods: A literature search of three databases was performed to identify key studies on the frequency of germline and somatic variants in adult cancers and the extent to which they inform diagnosis, management and outcome. Findings were inductively mapped and narratively synthesised.

Results: Consolidated results from 95 original research papers showed that pathogenic germline (familial) variants are found in ~10% of adults with cancer, of whom 53%-61% are offered germline genotype-directed treatment. Importantly, 50% of germline carriers would not have satisfied the eligibility criteria for genetic testing and/or reported a negative family history. Actionable somatic variants occur in 27%-88% of cases, which markedly impact the diagnosis for cancers of unknown primary. Matched treatments were identified for 31%-48% of cancer patients, of whom 33%-45% received it. Response and survival rates were better in individuals receiving matched therapies compared to those receiving standard of care or unmatched therapies. Trials show that circulating tumour DNA (ctDNA) assays are feasible and sensitive. The relatively non-invasive ctDNA sample collection is appealing for cancers with inaccessible or unknown primary sites, and serial monitoring of residual disease and/or treatment response.

Conclusions: As matched therapies are underutilised due to declining patient condition and fewer prior therapies predicting better response rates, research is needed on the suitability of cancer genomic profiling as a frontline test.

Keywords: cancer; ctDNA; genetics; genomics; germline; narrative review; somatic.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**FIGURE 1**
Large multi‐cancer studies internationally that included germline and/or somatic genomic profiling.

**FIGURE 2**
Studies internationally that included ctDNA analysis in primarily advanced cancer cohorts.

**FIGURE 3**
Adult cancers associated with the highest frequency of germline variants.

See this image and copyright information in PMC

References

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Utility of Germline, Somatic and ctDNA Testing in Adults With Cancer

Affiliations

Utility of Germline, Somatic and ctDNA Testing in Adults With Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials