BlueCross BlueShield of Tennessee Medical Policy Manual

Proteogenomic Testing for Individuals with Cancer

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018


Proteogenomics refers to the integration of genomic, proteomic and transcriptomic information to provide a more complete picture of genome function. Proteogenomic testing can be differentiated from proteomic testing, in that proteomic testing can refer to the measurement of protein products alone, without integration of genomic and transcriptomic information. When protein products alone are tested, this is not considered proteogenomic testing. The current focus of proteogenomics is primarily on the diagnostic, prognostic, and predictive potential of proteogenomics in various cancers. One commercial test (GPS Cancer™ Test) is available. The test includes whole-genome sequencing (20,000 genes, 3 billion base pairs), whole transcriptome (RNA) sequencing, and quantitative proteomics by mass spectrometry. The test is intended to inform personalized treatment decisions for cancer, and treatment options are provided when available, although treatment recommendations are not. Treatment options may include FDA approved targeted drugs with potential for clinical benefit, active clinical trials of drugs with potential for clinical benefit, and/or available drugs to which cancer may be resistant.




There is no published evidence on the clinical validity or clinical utility of proteogenomic testing (e.g., GPS Cancer™ Test), and only a few studies have provided information on validity for proteomic research in general. Further research is needed to adequately standardize and validate proteogenomic testing for clinical use.


BlueCross BlueShield Association. Evidence Positioning System. (7:2019). Proteogenomic testing for patients with cancer (2.04.140). Retrieved August 20, 2019 from (31 articles and/or guidelines reviewed)

Edwards, N. J., Oberti, M., Thangudu, R. R., Cai, S., McGarvey, P. B., Jacob, S., et al. (2015). The CPTAC data portal: A resource for cancer proteomics research. Journal of Proteome Research, 14 (6), 2707-2713. Abstract retrieved August 31, 2016 from PubMed database.

Gregorich, Z. R., & Ge, Y. (2014). Top-down proteomics in health and disease: challenges and opportunities. Proteomics, 14 (10), 1195-1210. (Level 4 evidence)

Jimenez, C., & Verheul, H. (2014). Mass spectrometry-based proteomics: from cancer biology to protein biomarkers, drug targets, and clinical applications. American Society of Clinical Oncology Educational Book, Volume 34, e504-e510. Retrieved August 27, 2018 from

Latonen, L., Afyounian, E., Jylhä, A., Nättinen, J., Aapola, U., Annala, M., et al. (2018). Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression. Nature Communications, 9, 1176. (Level 4 evidence)

Mertins, P., Mani, D., Ruggles, K., Gillette, M., Clauser, K., Wang, P., et al. (2016). Proteogenomics connects somatic mutations to signalling in breast cancer. Nature, 534 (7605), 55-62. (Level 4 evidence)

Sellappan, S., Blackler, A., Liao, W., O’Day, E., Xu, P., Thyparambil, S., et al. (2016). Therapeutically induced changes in HER2, HER3, and EGFR protein expression for treatment guidance. Journal of the National Comprehensive Cancer Network, 14 (5), 503-507. (Level 5 evidence)

Sheynkman, G., Shortreed, M., Cesnik, A., & Smith, L. (2016). Proteogenomics: integrating next-generation sequencing and mass spectrometry to characterize human proteomic variation. Annual Review of Analytical Chemistry, 9 (1), 521-545. (Level 4 evidence)

Zhang, H., Liu, T., Zhang, Z., Payne, S. H., Zhang, B., McDermott, J., et al. (2016). Integrated proteogenomic characterization of human high-grade serous ovarian cancer. Cell, 166 (3), 755-765. (Level 4 evidence)




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