Abstract 5429: Next generation sequencing of clinical samples from more than 4200 patients with myeloid malignancies
Authors: Jensen Taylor J. , Hoffman Heidi M. , Leo Angela , Mooney Michael , Gardner Sabrina , Chen Wenjie , Nagan Narasimhan , Boles Deborah , Parker Scott , Richman Tamara J. , Letovsky Stanley , Dong Henry , Cai Li , Chenn Anjen , Eisenberg Marcia 
Published: September 2020

Abstract
Myeloid malignancies can be defined as a series of conditions associated with abnormal myeloid cell proliferation and/or differentiation. This group of disorders is heterogeneous and includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and others. These disorders are often driven by somatic mutations and the detection of genetic variants can have diagnostic, prognostic, and therapeutic relevance to the patient. A laboratory developed test (IntelliGEN Myeloid) based on a next generation sequencing (NGS) panel that targets mutations within 50 genes linked to myeloid malignancies was developed, validated, and clinically implemented. Within these genes, multiple variant classes including single nucleotide variants, insertions, and deletions were reported. Whole blood or bone marrow samples from more than 4200 patients were submitted for testing during the evaluation period. DNA was extracted from each sample and used as the template for creating targeted NGS libraries (ArcherDx, Boulder, CO) that were subsequently sequenced on Illumina DNA sequencers (Illumina, San Diego, CA). Results were reviewed, orthogonally confirmed unless previously validated, and reported by clinical laboratory directors. Herein, the anonymized results from this cohort are presented. While testing is ongoing and additional samples will be included in the final analysis, these data were censored to include 4270 patient samples with reported results at the time of submission. The median patient age in this cohort was 71 years with 56.9% being male. Actionable variants (reported as Tier-I/II) or variants of unknown significance (reported as Tier III) were identified in all 50 genes within the panel, consistent with a comprehensive panel being necessary to encompass the mutations contributing to the etiology of these diseases. In total, more than 4400 unique variants were observed in this sample cohort. Clinically or potentially relevant variants (Tier I, II, or III) were detected in the majority of patients tested (72.8%) with a mean of 3.3 variants reported per patient. The size of our cohort also enabled indication-specific evaluation of mutational profiles. In patients where the indication for testing included AML, the most commonly mutated genes were TET2, ASXL1, DNMT3A, and RUNX1 whereas that list included ASXL1, DNMT3A, SF3BP1, SRSF1, and TP53 in patients where MDS was listed as an indication for testing. Taken together, these data describe the clinical testing demographics, the mutational spectrum of myeloid malignancies in a large clinical cohort, and suggest that mid-size NGS panels may provide physicians with diagnostic, prognostic, and therapeutic information that can help facilitate patient care.
Citation Format: Taylor J. Jensen, Heidi M. Hoffman, Angela Leo, Michael Mooney, Sabrina Gardner, Wenjie Chen, Narasimhan Nagan, Deborah Boles, Scott Parker, Tamara J. Richman, Stanley Letovsky, Henry Dong, Li Cai, Anjen Chenn, Marcia Eisenberg. Next generation sequencing of clinical samples from more than 4200 patients with myeloid malignancies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5429.