Oncofusion

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Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q92-kmt2a-sarcoma

Nobody has ever asked whether a KMT2A-rearranged sarcoma needs menin: zero records, and the reason is that no model exists

also called menin dependence in KMT2A sarcoma · no menin test in KMT2A-rearranged sarcoma

The drugs that work in KMT2A leukaemia work by breaking a grip between KMT2A and a protein called menin. Nobody has ever tested whether that grip matters in the KMT2A sarcomas - not once, in any cell, in any mouse - and the reason is that no laboratory model of these tumours exists.

The same thing, for a scientist

Bounded absence, measured 2026-09-21. The query `("YAP1::KMT2A"[tiab] OR "YAP1-KMT2A"[tiab] OR "VIM::KMT2A"[tiab] OR "VIM-KMT2A"[tiab]) AND (menin[tiab] OR MEN1[tiab] OR LEDGF[tiab] OR PSIP1[tiab] OR DOT1L[tiab])` returns **0 records**, with the rule-67 positive controls clean through the identical query shape: the fusion-name group alone returns 14, the same group with `sarcoma[tiab]` returns 13, and the menin/LEDGF/DOT1L group alone returns 5,054. So the zero is an intersection, not a broken query. The absence is structural rather than bibliographic: `KMT2A[tiab] AND sarcoma[tiab] AND ("cell line"[tiab] OR "cell lines"[tiab] OR xenograft[tiab] OR organoid[tiab] OR "patient-derived"[tiab])` returns 3 records and none reports a model of this entity - the only system in the literature is immortalised fibroblasts transfected with fusion constructs. Archive check: elink from each of the seven primary entity papers to GEO returns zero datasets, and the one series with its own genome-scale data (22-case methylation) states it is available from the corresponding author on request rather than deposited. Class: `never-measured`.

Go deeper
The measurement
query (PubMed esearch, 2026-09-21)records
fusion names AND (menin OR MEN1 OR LEDGF OR PSIP1 OR DOT1L)0
fusion names alone (control)14
fusion names AND sarcoma (control, identical shape)13
menin OR MEN1 OR LEDGF OR PSIP1 OR DOT1L alone (control)5,054
KMT2A AND sarcoma AND (cell line OR cell lines OR xenograft OR organoid OR patient-derived)3, none a model of this entity
menin AND sarcoma11, all Ewing sarcoma or MEN1-syndrome sarcoma
DOT1L AND sarcoma3, none in this entity

Every query used one field tag per term. querytranslation was read back on each; the zero query's translation shows that PubMed normalises :: to -, so the two spellings collapse into one string and the group is effectively three distinct names, not four 1.

The name list, because the absence is bounded by it and not by the query: YAP1::KMT2A, YAP1-KMT2A, VIM::KMT2A, VIM-KMT2A, and separately KMT2A[tiab] AND sarcoma[tiab] (55 records, all titles reviewed for this beat). Not searched: MLL spellings of the sarcoma fusions, which do not appear in this literature, and the two single-case arrangements CBX6::KMT2A::PYGO1 and LDB1::KMT2A.

Which kind of absence this is, and what it costs to close

never-measured. No instrument has been pointed at the question, and the reason is specific: there is no cell line, no xenograft and no patient-derived model of KMT2A-rearranged sarcoma anywhere in the searched literature 2. The only experimental system that exists is immortalised human fibroblasts transfected with YKY, YAP1::KMT2A and KMT2A::YAP1 constructs 3 - which is enough to ask the menin question and was not used to ask it.

The archive route is also closed. elink from each of the seven primary entity papers to GEO returns zero datasets (checked 2026-09-21), so this is not a measured-not-analysed absence hiding in a deposition 2. The 22-case methylation series holds the only genome-scale data on the entity and states it is available from the corresponding author on request rather than deposited (see the counter-note on 2).

Cost to close: low. A menin co-immunoprecipitation from the existing fibroblast construct panel, with a KMT2A::AFF1-expressing line as the positive control, is a few weeks of bench work and would settle the prediction outright. That is written up as exp-menin-pulldown-on-yky-versus-kmt2a-aff1.

What this implies for the index fusion, by contrast

This project's menin-interface hypothesis has never had a negative control in the form of a KMT2A rearrangement that lacks the interface and transforms anyway. KMT2A-rearranged sarcoma is that control, sitting in the literature for six years, and the experiment that would use it has not been run. The absence is therefore not just a gap in sarcoma knowledge; it is a missing test of the central claim of this graph.

Facts and figures
absence classnever-measured
what is absentany measurement of menin, LEDGF/PSIP1 or DOT1L dependence, binding or occupancy in any KMT2A-rearranged sarcoma or any model of one
query("YAP1::KMT2A"[tiab] OR "YAP1-KMT2A"[tiab] OR "VIM::KMT2A"[tiab] OR "VIM-KMT2A"[tiab]) AND (menin[tiab] OR MEN1[tiab] OR LEDGF[tiab] OR PSIP1[tiab] OR DOT1L[tiab])
querytranslation("YAP1-KMT2A"[Title/Abstract] OR "YAP1-KMT2A"[Title/Abstract] OR "VIM-KMT2A"[Title/Abstract] OR "VIM-KMT2A"[Title/Abstract]) AND ("menin"[Title/Abstract] OR "MEN1"[Title/Abstract] OR "LEDGF"[Title/Abstract] OR "PSIP1"[Title/Abstract] OR "DOT1L"[Title/Abstract])
records0
date2026-09-21
toolPubMed E-utilities esearch
archive checkedGEO via elink from all seven primary entity PMIDs: zero linked datasets. Data-availability statements read for the two open-access series.
archive resultno deposition found; the only genome-scale data (22-case methylation) is stated to be available from the corresponding author on request
models availablenone; the only experimental system is immortalised fibroblasts transfected with fusion constructs. Bounded in the literature (E1-E2) and now at the repository (E4): Cellosaurus holds no sarcoma line mentioning KMT2A and no sclerosing epithelioid fibrosarcoma line of any genotype.
cost to closelow - a menin co-immunoprecipitation from the existing construct panel with a KMT2A::AFF1 positive control
closes withexp-menin-pulldown-on-yky-versus-kmt2a-aff1
repository checkedCellosaurus REST API, 2026-09-21: cc:"KMT2A" (592 lines, scored by disease), di:"Sclerosing epithelioid fibrosarcoma" (0), and cc: queries for YAP1::KMT2A, VIM::KMT2A and LDB1::KMT2A (0 each).
repository resultZero sarcoma or mesenchymal lines among the 592 KMT2A-commented lines, and zero lines of this disease at any genotype. Confirms models_available='none' by a route independent of the PubMed bound in E1-E2. Query trap recorded in E4's counter_evidence: hyphenated fusion names return unrelated engineered host lines because the tokens are OR-ed.
controls
fusion names AND sarcoma …13.0fusion names AND sarcoma (identical shape): 13fusion names alone14.0fusion names alone: 14menin/MEN1/LEDGF/PSIP1/DO…5,054menin/MEN1/LEDGF/PSIP1/DOT1L alone: 5054
controls — the numbers behind the chart
{
  "fusion names alone": 14,
  "fusion names AND sarcoma (identical shape)": 13,
  "menin/MEN1/LEDGF/PSIP1/DOT1L alone": 5054
}
name list searched
[
  "YAP1::KMT2A",
  "YAP1-KMT2A",
  "VIM::KMT2A",
  "VIM-KMT2A",
  "KMT2A[tiab] AND sarcoma[tiab] (55 records, all titles reviewed)"
]
name list not searched
[
  "MLL spellings of the sarcoma fusions (absent from this literature)",
  "CBX6::KMT2A::PYGO1",
  "LDB1::KMT2A"
]
How this could bite us back
  • An untested target is not an absent target. Recording that nobody has measured menin dependence here must not harden into 'menin is irrelevant in this entity' - the coordinate argument predicts it, and prediction is not measurement.
  • Conversely, the absence should not be used to justify a menin inhibitor on the grounds that it has not been ruled out. The exon map is a positive reason to expect no binding site, which is a stronger prior than ignorance.
Still open
  1. Are the immortalised fibroblast lines expressing YKY, YAP1::KMT2A and KMT2A::YAP1 still available from the group that made them? If so the menin question is a request away rather than a construct away.
  2. Is there a Cellosaurus or DepMap entry for any sarcoma line with a KMT2A fusion? The literature search says no model exists but a cell-line registry query was not run and would be a stronger bound.
  3. Does any of the four public methylation comparison cohorts used by the largest series contain an unrecognised KMT2A-rearranged sarcoma? That would be a measured-not-searched signal recoverable by compute alone.
Every source behind this entry (4)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Measured here 2026-09-21 by PubMed esearch with one field tag per term: the sarcoma KMT2A fusion names intersected with menin, MEN1, LEDGF, PSIP1 or DOT1L return 0 records, while the fusion-name group alone returns 14, the same group with sarcoma returns 13 and the menin/LEDGF/DOT1L group alone returns 5,054.

    PubMed E-utilities esearch, bounded-absence measurements for menin and KMT2A-rearranged sarcoma · National Center for Biotechnology Information · PubMed E-utilities 2026
    What this evidence cannot show

    Bounded to titles and abstracts on 2026-09-21; supporting figures and supplementary tables are not reached by esearch, and this project has previously found a load-bearing ChIP measurement invisible to a clean abstract-level zero. However, no paper in this literature is a functional study at all, so the risk of a hidden supplementary menin experiment is lower here than usual. The name list is given in full in the section above and the absence is bounded by that list, not by the query mechanics.

    Evidence that argues against this (1)
    • A zero here could reflect vocabulary rather than absence - a functional study might frame itself at the level of 'MLL' or 'the MLL-menin interaction' without naming the sarcoma fusion. The broader control KMT2A[tiab] AND sarcoma[tiab] returns 55 records, every title of which was reviewed for this beat, and none is a functional or dependency study of any kind. Massoth LR et al. 2020
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    Measured here 2026-09-21: KMT2A[tiab] AND sarcoma[tiab] AND ("cell line"[tiab] OR "cell lines"[tiab] OR xenograft[tiab] OR organoid[tiab] OR "patient-derived"[tiab]) returns 3 records, none describing a cell line or xenograft of KMT2A-rearranged sarcoma, and elink from each of the seven primary entity papers to the GEO datasets database returns zero linked datasets.

    PubMed E-utilities esearch, bounded-absence measurements for menin and KMT2A-rearranged sarcoma · National Center for Biotechnology Information · PubMed E-utilities 2026
    What this evidence cannot show

    elink recall from PubMed to GEO is known in this project to be incomplete (roughly 37.5% in one audit), so a zero from elink alone does not exclude a deposition; it was supplemented by reading the data-availability statements of the two open-access series, one of which states its data are available on request and the other of which carries no availability statement at all. A negative literature search for a cell line is weaker than a negative Cellosaurus query; that query has since been run and is recorded as E4, which confirms this bound at the repository.

    Evidence that argues against this (1)
    • The largest series did perform genome-scale DNA methylation profiling on 22 cases and used four public comparison datasets (GSE110697, GSE112308, GSE140686, EGAS00001007042), so genome-scale data on this entity DO exist - they are simply not deposited. That makes the methylation half of the absence measured-not-reported rather than never-measured, even though the menin-dependence half is genuinely never-measured. Warmke LM et al. 2025
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The one experimental system that exists for this entity is immortalised human fibroblasts expressing YAP1::KMT2A::YAP1, YAP1::KMT2A and KMT2A::YAP1 constructs, in which differentially upregulated genes overlapped those of YKY-expressing tumours and of previously reported YAP1 fusions, with Wnt and Hedgehog pathway enrichment.

    PMID 37246732DOI
    What this evidence cannot show

    Read from the abstract only; the full text is unreachable through all five of this project's routes (no PMCID, so fullTextXML, efetch db=pmc and the PMC HTML page are unavailable, and the Wiley DOI returns HTTP 403). So it is not known whether these lines were banked, whether they are available, or whether transformation was assessed - only that the constructs were made and profiled. An immortalised fibroblast is also not a sarcoma cell.

    Evidence that argues against this (1)
    • A transfected immortalised fibroblast may be the wrong system to ask a menin question in: menin is ubiquitously expressed and the KMT2A-menin interaction is not lineage-restricted, so a negative pulldown would be informative but a positive one in a fibroblast would not establish relevance to the tumour. The right control is a side-by-side with a leukaemic fusion in the same cells. Kurmasheva RT et al. 2020
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    Cellosaurus, the cell-line registry of record, holds 592 cell lines whose comments mention KMT2A and NOT ONE is a sarcoma or any mesenchymal tumour: the diseases are 507 childhood acute monocytic leukemia, 21 childhood B-ALL, 19 adult acute monocytic leukemia, 15 adult AML, 6 adult B-ALL and a tail of leukaemias, plus one lung adenocarcinoma and 10 lines with no disease recorded. Searching the entity's own diagnosis, di:"Sclerosing epithelioid fibrosarcoma", returns ZERO cell lines of any genotype, and fusion-level queries cc:"YAP1::KMT2A", cc:"VIM::KMT2A" and cc:"LDB1::KMT2A" each return zero. So the model absence is bounded at the repository as well as in the literature, and it is bounded twice over: no line carries these fusions, and no line of this disease exists at all.

    What this evidence cannot show

    Cellosaurus indexes lines that have been described somewhere, so it inherits the literature's blind spots rather than being independent of them; a line established but never published would be invisible to both routes. The 592 figure counts lines whose COMMENTS mention KMT2A, which includes engineered knockouts as well as fusion-positive patient lines, so it is an upper bound on KMT2A-relevant lines and the zero-sarcoma result is the load-bearing part. The disease facet relies on Cellosaurus having assigned the SEF diagnosis at all, and an SEF line filed under a parent term such as plain fibrosarcoma would be missed by the di: query, though it would still have had to appear in the KMT2A comment set to matter here, and did not. DepMap was not queried separately; DepMap draws its lines from this same registry.

    Evidence that argues against this (1)
    • A hyphenated free-text query for these fusions gives a FALSE POSITIVE that reads as a model existing. YAP1-KMT2A returns HAP1, MCF-7 and HCT 116, and KMT2A-YAP1 returns the identical three, which proves the hyphen is not read as a fusion and the tokens are being OR-ed; VIM-KMT2A returns a different set of three (HAP1, HCT 116, A-549) and LDB1-KMT2A returns zero, so the membership tracks token frequency rather than biology. A reader who ran the natural query and stopped at the first hits would conclude a YAP1-KMT2A cell line exists. Only the field-scoped cc: and di: queries give the real answer.
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