In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 2082-2082
Abstract:
EML4-ALK gene fusions are oncogenic drivers in non-small cell lung cancer (NSCLC). Liquid biopsies containing circulating tumor DNA (ctDNA), including EML4-ALK, can be used to study tumor dynamics with next-generation sequencing (NGS). However, the sensitivity of EML4-ALK detection in liquid biopsies varies between different pipelines and analysis tools. We developed an R/Bioconductor package, DNAfusion, which can be applied to BAM files generated by commercially available NGS pipelines, such as AVENIO. 48 blood samples from a training cohort consisting of 41 stage IV EML4-ALK positive NSCLC patients and 7 healthy controls were used to develop DNAfusion. DNAfusion detected EML4-ALK in significantly more samples compared to AVENIO (sensitivity = 61.0% vs. 36.6%, P = 0.046). The newly identified EML4-ALK positive patients were verified using droplet digital PCR. DNAfusion was subsequently validated in a blinded validation cohort comprising 24 EML4-ALK positive and 24 EML4-ALK negative stage IV NSCLC patients. DNAfusion detected significantly more EML4-ALK individuals in the validation cohort compared to AVENIO (sensitivity = 62.5% vs. 29.2%, P = 0.042). DNAfusion demonstrated a specificity of 100% in both the training and the validation cohorts. Monitoring EML4-ALK variants with AVENIO and DNAfusion in serial blood samples from 24 stage IV EML4-ALK positive patients during treatment (n = 72), revealed that DNAfusion can detect EML4-ALK variants at clinically critical timepoints, otherwise missed by AVENIO. Here we present DNAfusion, which increases sensitivity of EML4-ALK detection in liquid biopsies and can be implemented downstream of commercially available NGS pipelines. The high sensitivity of DNAfusion is a necessity for analytical tools used to monitor ctDNA in serial plasma samples in order to implement liquid biopsies in the clinic. The simplistic way of operating the R package makes it easy to set up in the clinical setting enabling wider expansion of liquid biopsy and NGS based diagnostics. Citation Format: Christoffer Trier Maansson, Emma Roger Andersen, Maiken Parm Ulhoi, Peter Meldgaard, Boe Sandahl Sorensen. DNAfusion: An R/Bioconductor package for increased sensitivity of detecting EML4-ALK gene fusions in liquid biopsies from cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2082.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2023-2082
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2023
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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