Summary & Overview

CPT 0543U: TruSight Oncology Comprehensive Tumor Genomic Profiling

CPT code 0543U represents a Proprietary Laboratory Analyses (PLA) code for the TruSight™ Oncology Comprehensive test from Illumina Inc., a next-generation sequencing assay that profiles DNA and RNA from tumor tissue across 517 cancer-associated genes. Nationally, this code signals growing use of comprehensive genomic profiling to inform targeted therapy selection, eligibility for clinical trials, and assessment of tumor mutation burden. Key payers in the analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare.

Readers will find a concise overview of what CPT code 0543U covers, the clinical and laboratory context for its use, and how it fits into molecular oncology testing workflows. The publication summarizes payer coverage patterns and benchmarking where available, highlights policy considerations relevant to PLA codes, and outlines clinical implications such as mutation detection scope and tumor mutation burden reporting. Data not available in the input for specific modifiers, taxonomies, ICD-10 pairings, and detailed payer policy language is noted as unavailable. This national-focused briefing is designed to inform billing, coding, and policy stakeholders about the technical scope and policy relevance of CPT code 0543U.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0543UCPTProprietary Laboratory Analysesnext-generation sequencingtumor genomic profilingtumor mutation burdenmolecular diagnostics

Billing Code Overview

CPT code 0543U is a Proprietary Laboratory Analyses (PLA) code that applies exclusively to the TruSight™ Oncology Comprehensive test from Illumina Inc. The assay analyzes DNA from tumor tissue to detect genetic alterations across 517 cancer-associated genes using next-generation sequencing. It detects single- and multi-nucleotide variants, insertions and deletions, and reports gene fusions and splice variants by incorporating RNA analysis. The test also calculates tumor mutation burden, which can inform understanding of tumor behavior and potential response to therapies.

Service type: Laboratory molecular diagnostic test (next-generation sequencing, tumor genomic profiling)

Typical site of service: Clinical or reference laboratory with specimens submitted from oncology clinics, hospital outpatient departments, or pathology services

Clinical & Coding Specifications

Clinical Context

A 62-year-old patient with a newly diagnosed metastatic non-small cell lung carcinoma (NSCLC) undergoes tumor biopsy. The oncology team requests comprehensive genomic profiling to identify actionable somatic alterations for targeted therapy selection and clinical trial eligibility. A formal pathology specimen (formalin-fixed, paraffin-embedded tumor tissue) is sent to the laboratory performing TruSight™ Oncology Comprehensive. The lab performs next-generation sequencing of tumor DNA and RNA to detect single-nucleotide variants, insertions/deletions, copy-number changes, gene fusions and splice variants across 517 cancer-associated genes, and calculates tumor mutation burden (TMB). The typical clinical workflow includes: specimen collection and accessioning at an outpatient clinic or hospital (ambulatory surgery center, hospital pathology lab, or reference lab), histologic confirmation of tumor content by a pathologist, extraction of nucleic acids, sequencing and bioinformatic analysis, and a finalized report returned to the ordering oncologist to guide systemic therapy selection or trial enrollment. Typical site of service: outpatient oncology clinic, hospital outpatient department, or reference molecular diagnostics laboratory. Service type: high-complexity molecular diagnostic laboratory testing (Proprietary Laboratory Analyses). Typical patient scenario: adult patients with advanced, recurrent, or metastatic solid tumors requiring broad genomic profiling for therapeutic and prognostic decision-making.

Coding Specifications

Modifier	Description	When to Use
`00`	No modifier required / billed as primary PLA code

Taxonomy Code	Specialty	Notes
`207RG0300X`	Hematology & Oncology	Medical oncologists order comprehensive tumor profiling for therapy selection.
`207Q00000X`	Anatomic/Clinical Pathology	Pathologists oversee specimen adequacy, testing indications, and interpretation.
`363L00000X`	Clinical Laboratory	Clinical laboratory directors and molecular diagnostics labs perform testing.
`2085R0201X`	Molecular Genetic Pathology	Specialists in molecular pathology managing NGS assays and report interpretation.
`207K00000X`	Surgical Oncology	Surgical oncologists may request testing after tissue resection for staging and therapeutic planning.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C34.90`	Malignant neoplasm of unspecified part of unspecified bronchus or lung	Lung cancers commonly undergo broad genomic profiling to identify targetable mutations.
`C50.912`	Malignant neoplasm of unspecified site of right female breast	Advanced breast cancers may be tested for actionable genomic alterations and TMB for therapy selection.
`C79.51`	Secondary malignant neoplasm of bone	Metastatic disease often prompts comprehensive profiling to guide systemic therapy.
`C18.9`	Malignant neoplasm of colon, unspecified	Colorectal cancers are commonly profiled for mutations and TMB relevant to targeted and immunotherapy choices.
`C61`	Malignant neoplasm of prostate gland	Advanced prostate cancers may be assessed for genomic alterations informing targeted treatments.
`C71.9`	Malignant neoplasm of brain, unspecified	Selected brain tumors may undergo molecular profiling for diagnostic and therapeutic planning.
`C80.1`	Malignant (primary) neoplasm, unspecified	Used when a malignancy is known but primary site or specific histology is pending; broad profiling can aid classification.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0543U`	TruSight™ Oncology Comprehensive; tumor DNA and RNA sequencing (Proprietary Laboratory Analyses)	Primary PLA code that describes comprehensive NGS testing of 517 genes, including mutation detection, fusion/splice variant identification, and tumor mutation burden calculation.
`88342`	Immunohistochemistry, per specimen; initial single antibody stain	Often performed on the tumor specimen to confirm tumor type and guide molecular testing eligibility prior to ordering comprehensive NGS.
`88305`	Level IV surgical pathology, gross and microscopic exam	Performed by pathologists to evaluate and report tumor histology and determine adequacy of tissue for molecular testing.
`81445`	Targeted genomic sequence analysis panel, 5-50 genes	Smaller gene panels that may be used as alternatives or reflex tests depending on clinical context; contrasts with the broader 517-gene PLA.
`0000F`	Genetic testing result interpretation (proprietary/per payer-specific reporting)	Example of ancillary professional interpretation/reporting services that may accompany complex molecular results (use depends on payer and reporting conventions).