Symbol for multiple potential partners in nomenclature

[ahwagner]

On today's call we discussed the symbol for representing "multiple possible partners" for a gene fusion. The initial proposal (see #5) included asterisk to represent this concept, but Gordana Raca proposed the alternative character "v" for alignment with its use in the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues:

The use of "v" as represented in the captured description t(v;11q23.3) appears to draw from the ISCN nomenclature for "variable", which in recent editions of ISCN is represented as "var" (though "v" does appear in these 2001 ISCN rules and perhaps intervening versions of the nomenclature). The use of "v" / "var" in translocations is not depicted explicitly in the ISCN nomenclature, but the above example is described by the WHO Classification as:

"a translocation between ... band 11q23.3 and any of a large number of fusion partners"

which appears analogous to the concept we are trying to represent.

It should be noted that the ISCN nomenclature states the following regarding the section on variation nomenclature:

The following sections outline a means to describe these variations; however, to avoid misinterpretation, it is strongly recommended that these variants not be included in ISCN nomenclature descriptions. Rather they should be reserved for report text descriptions as required. The variation may be useful to distinguish between two or more distinct cell lines or clones, e.g., chimerism or transplant.

[ahwagner]

Meanwhile, the proposed use of * as the character for representing the multiple possible partners concept was considered "more intuitive" by the participants on today's call, but concerns were voiced about the potential for challenges of using a symbol character in various systems.

We are currently seeking examples of where the use of * within the nomenclature may be problematic; participants are encouraged to draw from use cases where the same character is used (or similarly excluded in favor of "Ter") to represent sequence termination in HGVS.

[ahwagner]

From Gordana re: v character:

I don't think they took it straight from ISCN, because (if I understand correctly) ISCN uses 'var' differently, to indicate variable regions on chromosomes (regions that show variation in morphology as a form of benign population variation, for example variable size of the heterochromatin region on the Y chromosome). I did not see just 'v' in the list of ISCN symbols (I attached an old list of symbols from ISCN 1996, i don't have ISCN2020 handy, but I checked that 'v' was not on the list). I don't know if we need to worry about confusion between 'v' as variable gene partner and 'var' in ISCN as a variable chromosome region? Otherwise 'v' has advantage that WHO used it (I can look for more examples in the book) and they are a big authority. We could wait to see what other comments we get on the use of 'v' for variable fusion partners.

ISCN Symbols and Abbreviated Terms[49].pdf

[ahwagner]

Resolution: Yassmine to reach out about upcoming WHO guidelines and confirm continued use of "v", if so, we will persist this as our own recommendation for the analogous concept.