Medical Policy


Subject: Molecular Profiling and Proteogenomic Testing for the Evaluation of Malignant Tumors
Document #: GENE.00025 Publish Date:    03/29/2018
Status: Reviewed Last Review Date:    11/02/2017


This document addresses molecular profiling and proteogenomic testing for the evaluation of malignant tumors. Commercially available molecular profile tests or panels include, but may not be limited to:

At the present time, there is at least one commercially available proteogenomic test in the United States, the Genomic Proteomic Spectrometry, or GPS Cancer test (NantHealth [Culver City, CA]).

When an individual genetic test included in a profile is separately addressed in a separate medical policy, that policy document applies.

Note: For additional information please see the following related documents:

Position Statement

Investigational and Not Medically Necessary:

Molecular profiling as a method to guide the selection of therapeutic agents for malignant tumors is considered investigational and not medically necessary.

Proteogenomic testing (for example, the GPS Cancer test) is considered investigational and not medically necessary for all indications.


Molecular Profiling

Molecular profiling for malignant tumors catalogues specific biomarker information and generates potential treatment options. The personalized tumor molecular profiling services or test panels addressed in this document are similar in that they all evaluate tumor tissue and, from it, produce a molecular profile of the tumor and a list of potential therapies. However, their individual testing methods vary from matching over expressed genes with drugs to more complex systems biology approaches.

Foundation One

Foundation One uses next generation sequencing “to interrogate the entire coding sequence of 236 cancer-related genes (3769 exons) plus 47 introns from 19 genes frequently altered or rearranged in cancer.” Foundation One helps match the genomic alterations present in a tumor with specific targeted therapies or clinical trials. Recent small studies (Drilon, 2013; Lipson, 2012; Vignot, 2013) have investigated next generation sequencing in individuals with lung cancer. Others have used next generation sequencing in those with breast cancer (Ross, 2013a); colorectal and other gastrointestinal cancers (Dhir, 2017; Gong, 2017; Lipson, 2012), ovarian cancer (Ross, 2013b), and prostate cancer (Beltran, 2013). Limitations of these studies include small sample sizes and lack of randomization.

Molecular Intelligence Service or Target Now

A widely used tumor molecular profile has been the Target Now Molecular Profiling Service (Caris Life Sciences). According to the Caris Life Sciences website, their tumor profiling service is now being promoted as the Molecular IntelligenceService. The published literature addressing these services is limited. Von Hoff and colleagues (2010) evaluated 86 individuals with refractory metastatic cancer. Progression-free survival (PFS) using a treatment regimen selected by Target Now molecular profiling of a malignant tumor was compared with the PFS of the most recent treatment regimen on which the individual experienced progression. A molecular target was detected in 84 of 86 (98%) participants. A total of 66 (78.6%) individuals were treated according to the molecular profile results with 18 of the 66 (27%) having a PFS ratio (defined as PFS on molecular profile–selected therapy or PFS on prior therapy) of greater than or equal to 1.3 (95% confidence interval [CI], 17% to 38%; p=0.007).

An editorial (Doroshow, 2010) accompanying the study reported that the trial had a number of significant limitations, including uncertainty surrounding the achievement of time to progression (the study’s primary endpoint), and a lack of a randomized design. Additional limitations include a small number of participants and lack of duplication of study results by an independent dataset.

Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)

Cheng and colleagues (2015) developed and evaluated the MSK-IMPACT, “a hybridization capture-based assay targeting all coding regions of 341 oncogenes and tumor suppressors.” The ability of the assay to detect single nucleotide variants (SNVs) and short insertions and deletions (indels) was assessed in 284 known positive solid tumor samples. Of these, 75 had a matched normal sample available. The authors reported successful detection of known variants in all 284 cases, and ability to achieve high degrees of resolution and levels of coverage to > 500x in tumor samples that allows low-frequency mutations to be detected. Current MSK-IMPACT efforts are focused on improvements to the analysis framework.

Other Molecular Profiling

Other molecular profiling such as GeneKey, GeneTrails Solid Tumor Panel, Guardant 360 Panel, OnkoMatch, OncInsights and SmartGenomics have less published validation. To date, there is insufficient peer-reviewed evidence specifically validating these tests.

In 2012, Tsimberidou and colleagues developed a personalized medicine program at a single facility in the context of early clinical trials. Their goal was to observe whether molecular analysis of advanced cancer and use of targeted therapy to counteract the effects of specific aberrations would be associated with improved clinical outcomes. Participants with advanced or metastatic cancer refractory to standard therapy underwent molecular profiling. A total of 175 subjects were treated with matched therapy, and the overall response rate was 27%. Of the 116 subjects treated with non-matched therapy, the response rate was 5%. The median time-to-failure was 5.2 months for those on matched therapy versus 2.2 months on non-matched therapy. At a median of 15 months follow-up, median survival was 13.4 months versus 9.0 months in favor of matched therapy.

Jameson and colleagues (2013) performed a small pilot study investigating multi-omic molecular profiling (MMP) for the selection of breast cancer treatment. MMP treatment recommendations were selected in 25 cases and original treatment plans were revised accordingly. Partial responses were reported in 5/25 (25%), stable disease in 8/25 (32%) and 9/25 had no disease progression at 4 months. This study was limited by its small size and non-randomization. A large randomized prospective trial is needed for further evaluation.

Primarily marketed to researchers, Life Technologies Inc. offers several variations of their Ion Torrent™ Next Generation Sequencing Ion AmpliSeq™ panels, according to the company website. The Ion AmpliSeq Comprehensive Cancer Panel analyzes more than 400 cancer-related genes and tumor suppressor genes. The Ion AmpliSeq Cancer Hotspot Panel v2 analyzes the “hotspot” regions of 50 cancer-related and tumor suppressor genes.

Randomized Controlled Trial of Molecularly Targeted Therapy

LeTourneau and colleagues (2012, 2015) reported on an open-label, randomized controlled phase II trial of treatment of refractory metastatic solid tumors directed by molecular profiling versus standard of care treatment.(SHIVA trial). A total of 195 adults, consisting of 99 in the experimental group and 96 in the control group, were enrolled from eight academic centers in France. The primary outcome was progression-free survival (PFS) analyzed by intention-to-treat. Randomization was stratified by three molecular pathways (hormone receptor pathway, PI3K/AKT/mTOR pathway, and RAF/MEK pathway). Molecular analysis included targeted next generation sequencing (NGS), gene copy number alterations and hormone expression by immunohistochemistry. The molecularly targeted drugs used in the experimental group were approved for clinical use in France, but were outside their indications. The control group received standard treatment chosen by the physician. Median follow-up was 11.3 months for both the experimental and control groups at the time of primary analysis of PFS. Median PFS was 2.3 months (95% CI, 1.7-3.8) in the experimental group versus 2.0 months (95% CI, 1.7-2.7 months) in the control group (hazard ratio, 0.88; 95% CI, 0.65-1.19; p=0.41). Upon subgroup analysis, there was no statistically significant difference in PFS between the two groups. Objective responses were reported for 4 of 98 (4.1%) assessable subjects in the targeted treatment group versus 3 of 89 (3.4%) assessable subjects in the standard care group. Among the safety population, grade 3-4 adverse events were reported for 43 of the 100 subjects (43%) who received a molecularly targeted agent and 32 (35%) of 91 subjects treated in the control group. The authors suggested that “off-label use of molecularly targeted agents should be discouraged and enrollment in clinical trials should be encouraged to help identify predictive biomarkers of efficacy.”

Other Considerations

The National Comprehensive Cancer Network (NCCN) guidelines do not contain recommendations for the general strategy of testing a tumor for a wide range of mutations. However, the guidelines do contain recommendations for specific genetic testing for individual cancers, when there is a known drug-mutation combination that has demonstrated benefits for that particular type of tumor, such as colon or non-small cell lung cancer.


In summary, there is insufficient published evidence to support the use of molecular profiling to guide treatment decisions for malignant tumors. The available published literature consists of one randomized controlled trial, a small number of uncontrolled studies and non-randomized trials that use imperfect comparators. This evidence is not sufficient to make any conclusions on clinical utility.


Proteogenomics refers to the complex integration of genomic, proteomic and transcriptomic data to provide a more comprehensive picture of the function of the genome. Proteogenomic testing differs from proteomic testing, in that proteomic testing is typically limited to the measurement of protein products alone, without the inclusion of genomic and transcriptomic information.

Research on the use of proteogenomic testing for individuals with oncologic conditions is in the early stages of development and has primarily focused on the diagnostic, prognostic, and predictive value of proteogenomics in various cancers. A commercially available proteogenomic test in the United States is the GPS Cancer test (NantHealth [Culver City, CA]).

GPS Cancer Test

At the time of this review, no peer-reviewed published evidence on the clinical validity or utility of the GPS Cancer test and no guidelines or recommendations by professional medical societies or governmental organizations addressing the GPS Cancer test were identified.

Several studies have been published in the past few years on whole exome and tumor-normal sequencing, which may be applicable one component of the GPS cancer test (Beltran, 2015; Jones; 2015; Mandelker, 2017; Teer, 2017).  These studies have described the ability of whole exome and tumor-normal sequencing to identify individuals within a population with inheritable genetic mutations with potential clinical ramifications, including the identification of mutations for which specific pharmacological therapies are available, in a rare percentage of the time.  However, the methods used are not the same as the GPS test and these studies do not provide any data related to clinical or health-related outcomes that may result from the use of whole exome and tumor-normal sequencing, let alone the GPS test.  These remain outstanding questions that need to be addressed in properly designed and conducted trials.Conclusion

There is insufficient information to draw conclusions regarding the clinical validity or utility of the GPS Cancer test in the diagnosis, prognosis or management of individuals with oncologic conditions. Additional research is needed to determine if the GPS Cancer Test results in improved health outcomes and which population of individuals with oncologic conditions might benefit from proteogenomic testing using the GPS Cancer test.


Cancer is a significant health problem in the United States. The American Cancer Society estimates that in 2016, there will be 1,685,210 new cancer cases diagnosed and 595,690 cancer deaths in the US. In general, tumor location, stage, grade, and the individual’s underlying physical condition have been used in the clinical setting to determine the specific therapeutic approach to a certain cancer.

Molecular Profiling

The use of individual molecular markers in cancer management is well established; however, the use of molecular profiling to evaluate malignant tumors is evolving. The rationale for molecular profiling is that more complete knowledge of molecular marker status may alter treatment provided and possibly improve individual outcomes. The use of molecular profiling to assist in making treatment decisions for individuals is evolving; however, strong evidence to support clinical effectiveness is not currently available. Examples of commercially available multiple molecular testing panels are described below.

Foundation One is a genomic profile intended to supplement traditional cancer treatment decision tools by matching each person tested with targeted therapies relevant to the molecular changes in their tumor. The company, Foundation Medicine retrieves the tumor sample from the pathology laboratory, sequences and analyzes the tumor and sends an interpretive report for each person tested. The report highlights molecular changes that may potentially guide therapy and provide scientific and medical literature to evaluate potential treatment options.

Molecular Intelligence Service or Target Now Molecular Profiling Service begins with an immunohistochemistry analysis and if there is a frozen sample of tumor tissue available, a gene expression analysis by microarray may be performed. Additional tests may be added including: fluorescent in-situ hybridization to examine gene copy number variation in the tumor; polymerase chain reaction or deoxyribonucleic acid (DNA) sequencing is used to determine gene mutations in the DNA tumor. The results from each test are then applied to the published findings from cancer researchers and potential treatment options are subsequently generated. The Molecular Intelligence Service is promoted in a similar manner and is said to be available in several levels of service, “allowing the physician to customize the level of profiling they deem necessary for each patient.”

GeneKey profiles a tumor genome through whole genome mRNA expression profiling and copy number variant detection. A fresh biopsy specimen is initially obtained and sent to a laboratory that runs GeneKey-specified tests. Analysis is performed by proprietary systems biology approaches. A scientific team from GeneKey is sent to present results of potential treatment options, scientific rationale and relevant literature citations to the treating physician and the individual being tested.

OncInsights also begins with a fresh tumor sample obtained by biopsy. The lab processes the sample measuring genes and molecular data points to create a molecular pathway map of the individual’s disease. The data is then processed by the company’s bioinformatics platform, which analyzes information using a series of algorithms to identify key drug targets or signatures of drug response/resistance. The individual’s unique profile is then compared to molecularly targeted drug databases to align disease characteristics with potential treatment options. Related scientific and clinical evidence are then located and a personalized report is generated.

The GeneTrails Solid Tumor Panel provides information for 37 genes known to have mutations in solid tumors. For 20 of the 37 genes, the presence of a mutation might justify the use of an FDA-approved therapeutic and 17 have mutations that might support clinical trial eligibility.

The Guardant360 panel analyzes 70 genes associated with a wide variety of solid tumors; however, there is a lack of published studies that evaluate the analytic validity of this technique.

OnkoMatch is a polymerase chain reaction (PCR) ‒based gene panel that detects 68 mutations (single nucleotide polymorphisms) in 14 oncogenes and tumor suppressor genes that are associated with solid tumors.

The Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) is a hybridization capture-based NGS assay that detects mutations, variants, and structural rearrangements. The MSK-IMPACT test offers paired analysis of solid tumor tissue with matched normal tissue to determine somatic cancer mutations to guide treatment decisions.

SmartGenomics is a cancer specific test consisting of multiple diagnostic panels targeting a variety of cancers including lung, colon, brain and thyroid cancer. The service provider, PathGroup indicates that results will assist physicians “to make more precise therapeutic recommendations and clinical management decisions.”


Whereas genomic study examines all of the genes of an organism, proteomic study addresses all of the proteins expressed by those genes. Proteogenomics combines proteomic and genomic data. In this approach, customized protein sequence databases employ genomic and transcriptomic information to help identify novel peptides not found in reference protein sequence databases. The proteomic data provides protein-level evidence of gene expression and helps to refine gene models. Due in large part to the emergence of next generation sequencing technologies such as RNA sequencing and improvements in the depths and throughput of mass spectrometry-based proteomics, the pace of proteogenomics research has greatly accelerated (Nesvizhskii, 2014).

Proteogenomics may someday provide a detailed analysis of the molecular components and underlying mechanisms associated with the development of various cancers. This work is driven in part by the hypothesis that a better understanding of both proteomics and genomics will improve diagnosis and treatment decisions in individuals with oncologic conditions. Potential clinical applications of proteogenomics include, but are not limited to:

According to information on the NantHealth website, the GPS Cancer test integrates quantitative targeted proteomics detected by mass spectrometry with whole transcriptome and whole genome sequencing, of both cancer tissue and normal tissue. The GPS Cancer test is marketed as a tool to diagnose molecular alterations in an individual’s cancer, and to identify personalized therapeutic regimens.

The White House Office of the Vice President of the United States has announced an international collaboration between the National Cancer Institute (NCI) at the National Institutes of Health in the United States, and Macquarie University, Children's Medical Research Institute, Garvan Institute of Medical Research, and Bioplatforms Australia Limited in Australia, to facilitate scientific collaborations in the field of clinical proteogenomic studies and their translation to cancer care. Additionally, the State governments of New South Wales and Victoria have signed separate agreements with the NCI that will construct a general framework of collaboration for promoting and conducting high-quality research and data-sharing to strengthen the evidence base necessary for cancer prevention, treatment, and management. As part of the Cancer Moonshot, it is hoped that this international partnership will break down silos and allow scientists to work together and share information, with the goal of ending cancer as we know it (NCI, 2016).

As a result of the interest in proteogenomic research, several databases are under construction. These databases include but are not limited to the Human Protein Reference Database, Human Cancer Proteome Variation Database and the Cancer Mutant Proteome Database.

Other Considerations

The services or tests addressed in this document have not been approved by the United States Food and Drug Administration (FDA). However, the labs that perform the tests are certified under the federal Clinical Laboratory Improvement Amendments (CLIA) of 1988 and do not require FDA approval to be sold.


Cancer Moonshot: A collaborative effort between the public and private sectors (including but not limited to the governments, researchers, healthcare providers, data and technology experts, patients, families, and patient advocates) to make a decade’s worth of advances in the understanding, prevention, diagnosis, treatment, and care of cancer in 5 years beginning in 2016.

Copy number variant: An alteration of the DNA of a genome that results in the cell having an abnormal number of copies of one or more sections of the DNA.

Genome: The total genetic composition of an organism.

Genomic data: Information derived from the sequencing of DNA or RNA fragments.

Immunohistochemistry: The process of detecting proteins in the cells of a tissue section.

Indel: A genomic insertion or deletion.

Messenger ribonucleic acid (mRNA): A molecule that results when a cell "reads" a DNA strand.

Molecular profiling services: Laboratory services which catalogue a number of genetic markers in an attempt to select optimal therapy.

Next-generation sequencing: Any of the technologies that allow rapid sequencing of large numbers of segments of DNA, up to and including entire genomes.  

Proteome: The complete set of proteins expressed by a genome.

Proteomic data: Data related to the functioning of protein; generally obtained using a combination of liquid chromatography and tandem mass spectrometry.

Proteomics: The comprehensive and integrative study of proteins and their biological functions.

Transcriptome: The sum total of all the messenger RNA molecules expressed from the genes in a specified cell population or organism. May also be defined as the array of mRNA transcripts expressed in a particular cell or tissue type.

Whole genome (DNA) sequencing: A laboratory procedure which seeks to determine an individual's entire DNA sequence, specifying the order of every base pair within the genome at a single time. Also known as full genome sequencing (FGS), complete genome sequencing, or entire genome sequencing.

Whole transcriptome (RNA) sequencing: A next-generation sequencing technique used to identify and measure RNA in a biological sample at a given moment in time. Also known as RNA sequencing and whole transcriptome shotgun sequencing.


The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.




Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis


Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, NRAS, MET, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed


Targeted genomic sequence analysis panel, hematolymphoid neoplasm or disorder, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, BRAF, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KRAS, KIT, MLL, NRAS, NPM1, NOTCH1), interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed


Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm, DNA analysis, and RNA analysis when performed, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MLL, NPM1, NRAS, MET, NOTCH1, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed


Unlisted molecular pathology procedure [when specified as molecular profiling for malignant tumors or proteogenomic testing such as the GPS Cancer test]


Unlisted multianalyte assay with algorithmic analysis [when specified as molecular profiling for malignant tumors]


Examination and selection of retrieved archival (ie, previously diagnosed) tissue(s) for molecular analysis (eg, KRAS mutational analysis) [when in conjunction with molecular profiling for malignant tumors]


Oncology (solid organ neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, fresh or frozen tissue or cells, report of specific gene rearrangement(s)
MatePair Targeted Rearrangements, Oncology, Mayo Clinic


Hematology (hematolymphoid neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, whole blood or bone marrow, report of specific gene rearrangement(s)
MatePair Targeted Rearrangements, Hematologic, Mayo Clinic


Exome (ie, somatic mutations), paired formalin-fixed paraffin-embedded tumor tissue and normal specimen, sequence analyses
EXaCT-1 Whole Exome Testing; Lab of OncologyMolecular Detection, Weill Cornell Medicine Clinical Genomics Laboratory


Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes, interrogation for sequence variants, gene copy number amplifications, gene rearrangements, microsatellite instability and tumor mutational burden
FoundationOne CDx™ (F1CDx); Foundation Medicine, Inc.



ICD-10 Diagnosis



Malignant neoplasms


Hodgkin and non-Hodgkin lymphomas


Peer Reviewed Publications:

  1. Ansong C, Purvine SO, Adkins JN, et al. Proteogenomics: needs and roles to be filled by proteomics in genome annotation. Brief Funct Genomic Proteomic. 2008; 7(1):50-62.
  2. Armengaud J. A perfect genome annotation is within reach with the proteomics and genomics alliance. Curr Opin Microbiol. 2009; 12(3):292-300.
  3. Beltran H, Eng K, Mosquera JM, et al. Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. JAMA Oncol. 2015; 1(4):466-474.
  4. Beltran H, Yelensky R, Frampton GM. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013; 63(5):920-926.
  5. Cheng DT, Mitchell TN, Zehir A, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015; 17(3):251-264.
  6. Dhir M, Choudry HA, Holtzman MP, et al. Impact of genomic profiling on the treatment and outcomes of patients with advanced gastrointestinal malignancies. Cancer Med. 2017; 6(1):195-206.
  7. Doroshow JH. Selecting systemic cancer therapy one patient at a time: is there a role for molecular profiling of individual patients with advanced solid tumors? J Clin Oncol. 2010; 28(33):4869-4871.
  8. Drilon A, Wang L, Hasanovic A. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov. 2013; 3(6):630-635.
  9. Garber K. Ready or not: personal tumor profiling tests take off. J Natl Cancer Inst. 2011; 103(2):84-86.
  10. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012; 366(10):883-892.
  11. Gong J, Cho M, Sy M, et al. Molecular profiling of metastatic colorectal tumors using next-generation sequencing: a single-institution experience. Oncotarget. 2017; 8(26):42198-42213.
  12. Huang PJ, Lee CC, Tan BC, et al. CMPD: cancer mutant proteome database. Nucleic Acids Res. 2015; 43(Database issue):D849-855.
  13. Jameson GS, Petricoin EF, Sachdev J, et al. A pilot study utilizing multi-omic molecular profiling to find potential targets and select individualized treatments for patients with previously treated metastatic breast cancer. Breast Cancer Res Treat. 2014; 147(3):579-588.
  14. Jones S, Anagnostou V, Lytle K, et al. Personalized genomic analyses for cancer mutation discovery and interpretation. Sci Transl Med. 2015; 7(283):283ra53.
  15. Keshava Prasad TS, Goel R, Kandasamy K, et al. Human Protein Reference Database--2009 update. Nucleic Acids Res. 2009; 37(Database issue):D767-772.
  16. Le Tourneau C, Delord JP, Gonçalves A, et al.; SHIVA Investigators. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015; 16(13):1324-1334.
  17. Le Tourneau C, Kamal M, Trédan O, et al. Designs and challenges for personalized medicine studies in oncology: focus on the SHIVA trial. Target Oncol. 2012; 7(4):253-265.
  18. Lipson D, Capelletti M, Yelensky R. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012; 18(3):382-384.
  19. Mandelker D, Zhang L, Kemel Y, et al. Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline testing.  JAMA. 2017; 318(9):825-835.
  20. Mukherjee S, Ma Z, Wheeler S, et al. Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors. Cancer Genet. 2016; 209(4):119-129.
  21. Nesvizhskii AI. Proteogenomics: concepts, applications and computational strategies. Nat Methods. 2014; 11(11):1114-1125.
  22. Renuse S, Chaerkady R, Pandey A. Proteogenomics. Proteomics. 2011; 11(4):620-630.
  23. Rivers RC, Kinsinger C, Boja ES, et al. Linking cancer genome to proteome: NCI's investment into proteogenomics. Proteomics. 2014; 14(23-24):2633-2636.
  24. Ross JS, Ali SM, Wang K. Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies. Gynecol Oncol. 2013a; 130(3):554-559.
  25. Ross JS, Wang K, Sheehan CE. Relapsed classic E-cadherin (CDH1)-mutated invasive lobular breast cancer shows a high frequency of HER2 (ERBB2) gene mutations. Clin Cancer Res. 2013b; 19(10):2668-2676.
  26. Subbannayya Y, Pinto SM, Gowda H, et al. Proteogenomics for understanding oncology: recent advances and future prospects. Expert Rev Proteomics. 2016; 13(3):297-308.
  27. Teer JK, Zhang Y, Chen L, et al. Evaluating somatic tumor mutation detection without matched normal samples. Hum Genomics. 2017; 11(1):22.
  28. Tsimberidou AM, Iskander NG, Hong DS, et al. Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res. 2012; 18(22):6373-6383.
  29. Vignot S, Frampton GM, Soria JC. Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. J Clin Oncol. 2013; 31(17):2167-2172.
  30. Von Hoff DD, Stephenson JJ Jr., Rosen P, et al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010; 28(33):4877-4883.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. NCCN Clinical Practice Guidelines in Oncology™. © 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: Accessed on October 3, 2017.
    • Colon cancer (V2.2017). March 13, 2017.
    • Non-small cell lung cancer (V7.2017). July 14, 2017.
Websites for Additional Information
  1. American Cancer Society. Available at: Accessed on October 4, 2017.
  2. Office of Cancer Clinical Proteomics Research, National Cancer Institute. What is Cancer Proteomics? Accessed on October 4, 2017.

Caris Life Sciences Molecular Intelligence Service
Caris Target Now
Caris Test
Foundation One
GPS Cancer Test
Ion Torrent Next Generation Sequencing Ion AmpliSeq
Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)
Multi-Omic Molecular Profiling (MMP)
Proteogenomic Test
Target Now Molecular Profiling Service

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History






Updated Coding section with 04/01/2018 CPT changes; added PLA codes 0036U, 0037U.



Medical Policy & Technology Assessment Committee (MPTAC) review.



Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale and References sections.



Updated Coding section with 08/01/2017 CPT PLA code changes



MPTAC review.



Hematology/Oncology Subcommittee review. Investigational and NMN statement added for proteogenomic testing. Description, Rationale, Background, Definitions, Coding, References and Index sections updated.



MPTAC review.



Hematology/Oncology Subcommittee review. Description, Background and Reference sections updated. Updated Coding section with 01/01/2016 CPT descriptor changes, and also removed ICD-9 codes.



MPTAC review.



Hematology/Oncology Subcommittee review. Rationale, Background, Reference and Index sections updated. Updated Coding section with 01/01/2015 CPT changes.



MPTAC review.



Hematology/Oncology Subcommittee review. Brand names removed from position statement. Description, Rationale, Background, Definition, and Reference sections updated.



MPTAC review.



Hematology/Oncology Subcommittee review. Position statement updated to include “Molecular Intelligence Service”. Description, Rationale, Background, Definition, Reference, and Index Sections updated.



Updated Coding section with 01/01/2013 CPT changes; removed 88384-88386 deleted 12/31/2012.



MPTAC review.



Hematology/Oncology Subcommittee review. Initial document development.