31. A cross-consortia initiative for aligning the definitions and descriptions of gene fusions

Abstract

Despite the well-established role of gene fusions in oncogenic processes, current practices for characterizing and annotating gene fusion events in the clinical setting and in biomedical literature are inconsistent. Consequently, evidence-based interpretation of functional and clinical significance of fusion variants requires laborious and time-consuming gathering and review of putative evidence. Differences between community standards inhibit the uniform communication of fusion events as well as the interoperability of tools, resources, and pipelines, ultimately impeding data sharing and downstream utility.

To address these challenges, a cross-consortia initiative between the Variant Interpretation for Cancer Consortium (VICC), CGC, ClinGen Somatic, and AMP was formed to develop a unified, standard nomenclature for representing the product of gene fusions (fusions.cancervariants.org). Invested participants across academic, government, and industry sectors engaged with these challenges to propose solutions via participation in community surveys and discussions to define and develop a standard for this diverse class of alterations. Our recent efforts to align these pre-release recommendations for fusion representation with the recommendations of the HGNC, ISCN, and HGVS nomenclature committees have resulted in consensus definitions and interoperable nomenclature systems for the description of gene fusions.

In January 2024, the first major release (21.0.0) of the HGVS nomenclature since 2020 includes the results of this work, which is also reflected in the cross-consortia recommendations. We discuss the vocabulary and nomenclature alignment between these related and cross-referenced standards, and provide recommendations for characterization and representation of gene fusions across these systems.