Molecular profiling is increasingly used to match patients with metastatic cancer to targeted therapies, but obtaining a high-quality biopsy specimen from metastatic sites can be difficult.
Patient samples were received by Perthera to coordinate genomic, proteomic and/or phosphoproteomic testing, using a specimen from either the primary tumour or a metastatic site. The relative frequencies were compared across specimen sites to assess the potential limitations of using a primary tumour sample for clinical decision support.
No significant differences were identified at the gene or pathway level when comparing genomic alterations between primary and metastatic lesions. Site-specific trends towards enrichment of MYC amplification in liver lesions, STK11 mutations in lung lesions and ATM and ARID2 mutations in abdominal lesions were seen, but were not statistically significant after false-discovery rate correction. Comparative analyses of proteomic results revealed significantly elevated expression of ERCC1 and TOP1 in metastatic lesions.
Tumour tissue limitations remain a barrier to precision oncology efforts, and these real-world data suggest that performing molecular testing on a primary tumour specimen could be considered in patients with pancreatic adenocarcinoma who do not have adequate tissue readily available from a metastatic site.
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We thank the Pancreatic Cancer Action Network for acquisition of tissue samples.
E.M.B., J.R.B., S.M., E.P. and M.J.P. all have equity and employment with Perthera. L.M.M. and L.R. have equity and employment at the Pancreatic Cancer Action Network. All other authors declare that they have no conflict of interest.
Ethics approval and consent to participate
The study protocol, amendments and informed consent forms were approved by the New England Institutional Review Board (Protocol # PCT-01-012). Investigators obtained informed consent from each participant or participant’s guardian prior to enrolment. The research was conducted in accordance with recognised ethical guidelines, including the Declaration of Helsinki, CIOMS, Belmont Report and U.S. Common Rule, as described during training in Good Clinical Practice guidelines (CITI Training).
No relevant funding was used for this project.
Archival study data used to produce the results reported in this article can be found at Perthera and the Pancreatic Cancer Action Network’s Know Your Tumor program.
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Brar, G., Blais, E.M., Joseph Bender, R. et al. Multi-omic molecular comparison of primary versus metastatic pancreatic tumours. Br J Cancer 121, 264–270 (2019). https://doi.org/10.1038/s41416-019-0507-5