Duke Expands Footprint in Next Gen Cancer Sequencing Tech

A special report by Duke Cancer Institute the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report

New Horizons

The Clinical Molecular Diagnostics Laboratory is currently poised to offer a larger, more comprehensive NGS profiling test to DCI patients with solid tumor cancers. This single tissue-based test, known as the pan-cancer “Elio” assay, covers single base changes, insertions, deletions, rearrangements, and amplifications in 500+ genes in solid tumor cancers, and, like the send-out vendors, can also detect high TMB and MSI. Like the lab's smaller test, this too will be conducted and analyzed in-house.

“One advantage to the Elio assay is that more genes are covered, but we also really like the idea of having control over our own data,” said Director of the BioRepository & Precision Pathology Center Shannon McCall, MD. “We will be generating the data from Elio in-house, and this data will feed smoothly into Epic as well as our Molecular Registry of Tumors database (Frameshift MRT) once we’ve built that interface internally.”

Medical Director of the DUHS Clinical Laboratories Michael Datto, MD, PhD, with McCall and Deak, partnered with Personal Genome Diagnostics (PGDx, a Labcorp subsidiary) for FDA clearance of the "Elio" test.

They supplied research samples from the BioRepository — 147 unique tissue specimens from more than 20 tumor types — that had already undergone diagnostic testing and these samples were then re-tested with the PGDx Elio assay.

The Elio assay performed well. Duke and PGDx investigators found a high degree of concordance between the new test results (using Elio) and previous test results (generated by the send-out testing partner). They published on this last year in the Journal of Molecular Diagnostics

“We wanted to be sure that the assay we chose would have similar performance to what the clinicians were getting from our current send-out partner before committing to an in-house solution for comprehensive genomic profiling in solid tumors,” notes Deak.

This is important, she explained, because “insurers require that laboratories demonstrate that every clinical test performed has proven clinical validity (diagnostic, prognostic, or theragnostic) before paying for the test.”

Deak said that the project team finalized the clinical validation — in the Clinical Molecular Diagnostics Laboratory — of the new, FDA-cleared panel in November and has created an interface with EPIC Beaker, which is currently being tested. (EPIC Beaker is the laboratory information system used by DUHS Clinical Labs.)

The Clinical Molecular Diagnostics Laboratory is also developing, for an early 2023 release, an in-house custom testing workflow to help clinicians determine whether sequencing variants detected in the patient’s tumor are germline (hereditary — in all cells of their body) or only present in their cancer cells. Traditionally this type of testing has been offered only by send-out vendors. This determination can change how a patient’s treatment is managed and, if hereditary, can be part of cancer risk assessment for other cancers in that patient and for cancer risk assessment in biological relatives.

In the Blood

The Clinical Molecular Diagnostics Laboratory — in partnership with the Clinical Cytogenetics, Flow Cytometry, and Immunohistochemistry laboratories — already has a robust NGS molecular testing mechanism in place to detect disease-specific diagnostic and prognostic molecular markers for lymphomas and leukemias. They offer an in-house Myeloid NGS test that’s used to detect the most frequently mutated regions of 75 target genes in myeloid disorders, including myeloid leukemias, as well as an in-house NGS Heme Fusion Panel that looks at RNA for identification of oncogenic fusions across 97 genes that drive blood cancers.

Deak says the lab team is currently working on a Lymphoid NGS Panel, which consists of the most frequently mutated regions of 71 gene targets involved in lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and lymphoplasmacytic lymphoma (LPL).

“Many of the patients who would benefit from the Lymphoid NGS panel are currently being served by either the in-house Myeloid NGS panel or a send-out panel, both of which have considerable overlap with the panel we’re developing,” Deak explains, “but there’s also novel content on the lymphoid panel that’s not on the myeloid panel.”

Why this stepped-up expansion in testing?

“Our willingness to invest in the development of this testing (in the Pathology Department and in Duke Health Laboratories) for our cancer patients, is based on our strong belief in the future of precision medicine and our immediate desire to deliver test results to our patients sooner and sooner on their care path,” says Datto. “In-house testing allows our patient to get results faster, get on the right drug sooner, or get into a clinical trial in the hopes of a response or even a cure. In-house testing supports our research mission across Duke, and also allows us to train the next generation of molecular pathologists and clinical scientists. Maintaining a strong on-site clinical molecular lab with the ability to do amazing things is part of what makes us Duke!”