minimal Common Oncology Data Elements (mCODE) Implementation Guide, published by HL7 International / Clinical Interoperability Council. This guide is not an authorized publication; it is the continuous build for version 4.0.0-ballot built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/fhir-mCODE-ig/ and changes regularly. See the Directory of published versions
mCODE includes genomics-related data elements needed to inform cancer assessment and treatment options. The profiles directly derive from the HL7 CGWG Clinical Genomics Reporting Implementation Guide (GRIG) STU2 release. The GRIG provides helpful foundational concepts and guidance for representing different types of genomics reports. mCODE assumes one is familiar with the GRIG content and uses this additional guidance to identify what is clinically actionable and minimal for the purpose of diagnosis, treatment, and monitoring of cancer patients.
Three profiles relate to the capture of clinical genomics data:
Additionally, the following GRIG profiles are optionally included in the mCODE bundle:
The diagram below illustrates the distinction within an mCODE bundle.
The mCODE example Bundle-gx-genomic-bundle-adam-anyperson
demonstrates a bundle containing resources conforming with the GRIG genomics report.
The GenomeX use case under the CodeX FHIR accelerator has a broader scope that is not limited to oncology-specific genomic tests, with the primary goal of validating the HL7 GRIG. However, it is widely recognized that the most prevalent and pervasive application for genomics and precision medicine is in the field of oncology. Consequently, there is a need for clarification and additional guidance between the mCODE FHIR IG.
A minimal set of genomics elements may vary based on the type of test. For example:
NOTE: The initial mCODE scope will be with somatic variants in gene panels with the intention that these elements will also serve as foundational for non-oncology use cases.
Despite the variations, there is a general list of common elements. The Electronic Medical Records and Genomics (eMERGE) program provides a good illustration of the sections found in a generalized pharmacogenomics report which includes pharmacogenomics. This conceptual representation serves as a good start for mCODE scoping but needs further guidance on how to specifically show certain representation patterns. These include the following patterns which will be covered in the sections to follow:
There is currently no general consensus on standardizing the ordering of next-generation sequencing (NGS) genomic tests. Regardless, mCODE provides some high level information on test codes that may be helpful for identifying tests.
The identity of non-genomic laboratory tests is typically represented by a Logical Observation Identifiers and Names (LOINC) code. However, many genomic tests and panels do not have LOINC codes, although some might have an identifier in the NCBI Genomic Testing Registry (GTR), a central location for voluntary submission of genomic test information by providers. While GTR is a viable source for identifying many genomic tests, the user should be aware that the GTR is not a single authoritative source since the test data is voluntarily updated. Standardization of codes for genomic tests is essential to facilitate data analysis of genomic tests, and should be a priority for the genomics testing community in the near future. Implementers should also note that, to conform to the requirements of the US Core Laboratory Result Profile, if a suitable LOINC exists, it must be used. If there is no suitable code in LOINC, then a code from an alternative code system such as GTR can be used.
The HL7 GRIG guidance on defining variants states support for two reporting patterns of specifying variants:
Although mCODE should support both formats, it is preferable to use HGVS nomenclature for coding and protein variants where possible.
A full representation of an HGVS variant SHOULD include the following:
NOTE: The FHIR IG publisher validates HGVS-notated variants included in the FHIR examples, however it is not intended to validate all possible variants as there is no single HGVS validation tool that comprehensively covers the most up-to-date recognized variants for a given reference sequence.
Every FHIR genomics resource referenced by a genomics report (e.g.: Variant, Diagnostic Implication, Therapeutic Implication), should include a date or datetime, even if there was only one date included in the genomic report for all results. Doing so simplifies the ability for the implementer to directly track changes in cases of a variant reclassification or reinterpretation.
A genomics report will oftentimes include the classification, or clinical significance, of a variant using a five-tier terminology from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) 2015 Guidelines for the interpretation of sequence variants. The five-tier terminology includes the following categories: pathogenic, likely pathogenic, uncertain significance, likely benign, and benign. In alignment with the GRIG, this is represented in the DiagnosticImplication profile as an Observation component, clinical-significance.
Some genomics reports are gene panels that include a list of genes that do not have relevant variants, otherwise known as pertinent negatives.
Represent pertinent negatives by creating one instance of GenomicVariant with the following representation:
LA9634-2 "Absent"
to Observation valueCodeableConceptA fusion gene is made by joining parts of two different genes. Fusion genes, and the fusion proteins that come from them, arise when part of the DNA from one chromosome moves to another chromosome. Fusion proteins produced by this change may lead to the development of some types of cancer (source: NCI Cancer Dictionary).
mCODE represents a fusion gene as an instance of GenomicVariant with the following changes:
The diagram below shows an example representation for the gene fusion BCR_ABL1:
The mCODE example genomic-variant-fusion
demonstrates the gene fusion representation.
NOTE: A fusion event that is related to two variants will be expressed as two separate variant instances. Both variants from the same fusion event can be included as DiagnosticReport.result slices under GenomicsReport.
The GRIG provides extensive guidance and examples for querying FHIR genomic reporting data. Some of the ones relevant to mCODE are listed below for convenience.
The following example FHIR query will retrieve all of a patient's variants reported for a given gene. Note that the gene is expressed as an HGNC identifier (e.g.: HGNC:11389 is the STK11 gene).
GET <fhir endpoint>/Observation?subject=cancer-patient-john-anyperson&code=69548-6&component-code=48018-6&component-value-concept=HGNC:11389
GET <fhir endpoint>/Observation?subject:Patient=123&code-value-concept=http://loinc.org|53037-8$http://loinc.org|LA6668-3&_include:iterate=Observation:derived-from