A Model Information Management Plan for Molecular Pathology Sequence Data Using Standards: From Sequencer to Electronic Health Record

Abstract

Incorporating genetic variant data into the electronic health record (EHR) in discrete computable fashion has vexed the informatics community for years. Genetic sequence test results are typically communicated by the molecular laboratory and stored in the EHR as textual documents. Although text documents are useful for human readability and initial use, they are not conducive for data retrieval and reuse. As a result, clinicians often struggle to find historical gene sequence results on a series of oncology patients within the EHR that might influence the care of the current patient. Second, identification of patients with specific mutation results in the EHR who are now eligible for new and/or changing therapy is not easily accomplished. Third, the molecular laboratory is challenged to monitor its sequencing processes for nonrandom process variation and other quality metrics. A novel approach to address each of these issues is presented and demonstrated. The authors use standard Health Level 7 laboratory result message formats in conjunction with international standards, Systematized Nomenclature of Medicine Clinical Terms and Human Genome Variant Society nomenclature, to represent, communicate, and store discrete gene sequence data within the EHR in a scalable fashion. This information management plan enables the support of the clinician at the point of care, enhances population management, and facilitates audits for maintaining laboratory quality.

Figure 1

Synoptic pathology report use case begins. An example Health Level 7 (HL7) message sent to the electronic health record (EHR) from the anatomic pathology system for a right hemicholectomy for a right colon mass signed out as a moderately differentiated colonic adenocarcinoma, 5 cm in greatest dimension and with invasion into the muscularis propria, three positive lymph nodes of 25 examined, and no perineural invasion identified. The anatomic pathology system reports synoptic observables to the EHR by the HL7 interface.

Figure 2

Next-generation sequencing pipeline to reporting to data use process flow. EHR, electronic health record; ID, identification; VCF, variant call format.

Figure 3

Molecular pathologist report of clinical significance. Clinical significance of each reported variant is as follows. Tier 1: KRAS c.34G>A variant is predicted to result in a substitution of glycine with serine at codon 12. It is known to confer reduced sensitivity to cetuximab/panitumumab in patients with colorectal cancers. Tier 2: In colon cancer, BRAF V600E does not confer any therapeutic advantages or disadvantages at this time. However, if there were a question about the possibility of a mismatch repair syndrome in this patient, then the presence of this variant indicates that this tumor is not related to a hereditary cancer predisposition syndrome because it is practically never seen in colon cancers of germline mismatch repair origin. Although the BRAF V600E is therapeutically actionable in melanomas and other tumors, it is not currently in colon cancer, but this could change in the future. APC c.2626C>T results in immediate truncation of the APC protein at codon 876, and this usually indicates worse function of this tumor suppressor function. However, this particular variant has been reported in multiple patients with familial adenomatous polyposis (FAP), and autosomal dominant inherited disorder and a member of the family of APC-associated conditions that predisposes patients to early development of colon cancer. Germline testing would be needed to determine whether variant represents a somatic change, full FAP, or attenuated FAP. Tier 3: MET c.3497G>A variant has no known diagnostic or therapeutic implications at this time, but this could change in the future.

Figure 4

Health Level 7 (HL7) version2.x coded molecular laboratory results of colon cancer sequence report to electronic health record.

Figure 5

Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) concept definition of KRAS nucleotide sequence detected in excised malignant neoplasm (observable entity).