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cancervariants / fusions

A repository for tracking documents, issues, and tools for the VICC / ClinGen gene fusion curation SOP
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Disambiguate language for chimeric transcripts and disregulated gene rearrangements #4

Closed ahwagner closed 2 months ago

ahwagner commented 3 years ago

Jie Liu (Cincinnati Children's) wrote on 9/23:

I have been struggling for a while about gene fusion scope/definition/nomenclature issues.

To have a standardized nomenclature for the fusion gene curation at the level of aggregate notation, I think we could follow the formats employed in 2016 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues to distinguish the two major categories within our scope. Here is what I summarized from this book.

“gene1-gene2 (5’ to 3’): a dash (-) is used to separate coding sequences between gene1 and gene2, which leads to a fusion protein, for example BCR-ABL1, ETV6-RUNX1, and many other examples, like page 77-78, and in contents pages. Of note, on page 30 under Synonyms section, it has “chronic granulocytic leukemia, BCR/ABL1” as a legacy name.

“gene1/gene2 (5’ to 3’)”: a slash (/) is used to separate the promoters/enhancer/noncoding region of gene1 from coding sequence of gene 2, which leads to dysregulation of gene 2 expression through juxtaposition effect. , for example IGH/BCL2 (page 14 and 272), IGH/IL3 (page 206), and others on page 242. However, a slash for such juxtapositioning effect of translocation was not used as commonly as a dash for chimeric proteins. TCR related translocation in T-ALL (page 211) and GATA2 and MECOM with inv (3) on page 138 were described in the paragraphs and not using slash as a final product.

ahwagner commented 3 years ago

On today's call, this issue was raised again independently. The suggestion was that we take the time to explicitly define these classes of "fusions" and provide guidance on their annotation and description. See comment above for one proposal from a 2016 WHO Classification guide for capturing this in a compact, human-readable nomenclature.