A46: Primary versus metastasis using iontorrent next generation sequencing (PRIMINGS)

David Moore1,2,Luke Martinson1,William Dalleywater2,Jacqui Shaw1,John Le Quesne1,2

1University of Leicester, Leicester, UK,2University Hospitals Leicester, Leicester, UK

Presenting date: Monday 2 November

Background

Cancer patients who have undergone tumour resection with curative intent often present subsequently with a tumour nodule at a distant anatomical site. In order to plan the most appropriate treatment it is vital to know whether this new lesion represents a metastasis from the original tumour, or a new primary cancer. Usually the new lesion is biopsied and a diagnosis is made on histology with immunohistochemical tests and consideration of the clinical context. No single immunohistochemical marker shows perfect sensitivity or specificity for specific tumour types however, and the new lesions are not infrequently diagnosed on 'best guess', based on discriminating pathological features, combined with the radiological and clinical findings.

Targeted next generation sequencing (NGS) has been shown to be useful in case reports of difficult cases but has not been tested on a series of clinical cases with a definitive diagnosis of second primary or metastatic tumour.

Method

Patients were selected from the recent diagnostic archive representing those with unequivocal dual primary tumours and confirmed primary and distant metastatic tumours. DNA was extracted from the archival tissue and tested using the Ion AmpliSeqTM Cancer Hotspot Panel v2.

Sequencing data was used to predict whether the second tumour represented a second primary or metastasis, blinded to clinical information.

Results

The pairs of primary and metastatic tumours showed common mutations, with sufficient overlap to predict confidently their shared clonal origin. The pairs of primary tumours showed differing mutational profiles. Prediction of separate primary or metastasis was possible without the need to test germline DNA.

Conclusion

In patients with a second distant tumour following cancer resection, identification of this as a metastasis or second primary tumour is a crucial clinical distinction. Targeted NGS has the potential to be a useful clinical test in these circumstances.