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Comparative Study
. 2019 Jul;121(3):264-270.
doi: 10.1038/s41416-019-0507-5. Epub 2019 Jul 11.

Multi-omic molecular comparison of primary versus metastatic pancreatic tumours

Gagandeep Brar  1 , Edik M Blais  2 , R Joseph Bender  2 , Jonathan R Brody  3 , Davendra Sohal  4 , Subha Madhavan  1   5 , Vincent J Picozzi  6 , Andrew E Hendifar  7 , Vincent M Chung  8 , David Halverson  2 , Sameh Mikhail  9 , Lynn M Matrisian  10 , Lola Rahib  10 , Emanuel Petricoin  2 , Michael J Pishvaian  11   12
Affiliations
Comparative Study

Multi-omic molecular comparison of primary versus metastatic pancreatic tumours

Gagandeep Brar et al. Br J Cancer. 2019 Jul.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
a Comparative frequencies of common mutations between metastatic lesions and primary pancreatic tumours. b Less common mutational frequencies between metastatic lesions and primary pancreatic tumours
Fig. 2
Fig. 2
a Comparative frequencies of genomic alterations between metastatic liver and lung lesions. b Comparative frequencies of genomic alterations between metastatic liver and abdominal lesions
Fig. 3
Fig. 3
Frequency heatmap comparing actionability of molecular alterations within the primary tumour site compared with metastatic sites (liver, abdomen and lung)
Fig. 4
Fig. 4
Comparative frequencies of protein and phosphoproteomic profiling between primary and metastatic tumours
Fig. 5
Fig. 5
a Comparative frequencies of protein and phosphoproteomic positivity between metastatic liver and lung lesions. b Comparative frequencies of protein and phosphoproteomic positivity between metastatic liver and abdominal lesions
See this image and copyright information in PMC

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