Every published KMT2A partner in sarcoma, counted - plus the papers this beat read and did not use, so the next beat does not repeat the search without the decisions
also called KMT2A sarcoma partner census · KMT2A-rearranged sarcoma enumeration
This is the full list of genes reported joined to KMT2A in soft-tissue sarcoma, how many cases each has, and what each contributes. It also records which papers were read and judged off-beat, so that a future reader can tell a paper that was dismissed from a paper nobody looked for.
The same thing, for a scientist
Census of published KMT2A fusion partners in soft tissue sarcoma as of 2026-09-21, and a bounded-rejection record for the beat. Recurrent partners: YAP1 (16 of 34 in the pan-sarcoma screen, plus 22 in the largest dedicated series, plus several later case reports - by far the commonest) and VIM (2 of 34, 4 published cases total). Single-case arrangements: CBX6::KMT2A::PYGO1 and LDB1::KMT2A. One cohort member carried PRRX1::KMT2D, a different gene. Sixteen further sarcomas in the pan-sarcoma screen carried unique non-recurrent partners, KMT2A 3' in eight and 5' in seven, with diverse histologies, median age 57 and 44% TP53 mutation, which the authors call of unclear significance and this graph treats as probable passengers. Partner functional classes represented: Hippo transcriptional co-activator, type III intermediate filament, chromobox/polycomb reader, LIM-domain transcriptional adaptor. NOT represented: any super elongation complex subunit, any DOT1L complex member, any P-TEFb or PAF1 complex component, any septin - i.e. none of the partner classes that dominate KMT2A leukaemia.
The census
| partner | cases | KMT2A contribution | architecture | partner class |
|---|---|---|---|---|
| YAP1 | 16/34 in the screen; 22 in the largest series; further case reports | exons 4/5-6 only (CXXC) | insertional YAP1::KMT2A::YAP1 | Hippo transcriptional co-activator 12 |
| VIM | 2/34; 4 published in total | exon 2 onward (aa 145-3969, SET intact) | conventional, KMT2A 3' | type III intermediate filament 13 |
| CBX6 / PYGO1 | 1 | not stated in the abstract | insertional CBX6::KMT2A::PYGO1 | chromobox (polycomb reader) / Pygopus 4 |
| LDB1 | 1 | exons 4-36 (aa 1053-3969, SET intact) | conventional, KMT2A 3' | LIM domain binding transcriptional adaptor 5 |
| KMT2D-PRRX1 (different gene) | 1 | n/a | n/a | recorded for completeness only 2 |
| 16 unique non-recurrent partners | 16/34 | 3' in 8, 5' in 7 | mixed, no reciprocal transcripts | diverse; probable passengers 1 |
The class that is missing is the finding. Of the four partner classes in this entity, not one is elongation machinery. In leukaemia, AFF1, AFF4, MLLT1, MLLT3, MLLT10 and ELL account for the overwhelming majority of partners and every one of them is an elongation or DOT1L-complex component. The sarcoma partners are transcription-factor adaptors, a chromatin reader and a cytoskeletal filament.
Bounded rejection: what was read and not used
Recorded so that a later cycle can tell a considered-and-dropped paper from one nobody looked for.
MLL[tiab] AND sarcoma[tiab]= 61 records, mostly dropped. Most are myeloid sarcoma - extramedullary acute leukaemia - which is a leukaemic deposit and not a soft tissue sarcoma. Dropped as a different disease. What would change my mind: a myeloid sarcoma case whose KMT2A breakpoint had the 3' polarity.- Ewing sarcoma menin papers (PMIDs 27888797, 33741715, 32333633, 29672864) - read, and used only as therapeutic context. They establish a wild-type MLL1/menin dependency downstream of EWSR1::FLI1, which is a different mechanism from a KMT2A fusion interface. Used in the trial-absence entry, not treated as evidence about this entity.
sclerosing epithelioid fibrosarcoma[tiab] = 222 records, largely dropped. The great majority are the conventional MUC4-positive, EWSR1/FUS::CREB3L-fused entity. Only the 14 that also mention KMT2A are on beat.- Thymoma / KMT2A::MAML2 reviews (PMIDs 38067300, 33674910) - read, not used. They concern a different non-haematologic KMT2A entity that this graph already holds as
disease-kmt2a-maml2-thymoma. Noted because one sarcoma case had concurrent KMT2A and MAML2 rearrangements by FISH 2, which is an unresolved loose end. - Soft-tissue pathology update reviews (PMIDs 34958510, 31686193, 38278601) - read as maps only. Useful for entity status; no primary data.
- PRRX1::KMT2D - enumerated and dropped. A different gene, and this graph's MLL2/MLL4 naming hazard makes a KMT2D claim expensive to state correctly. Not pursued.
- Papers found, on topic, and NOT readable: PMID 31136005 (Yoshida, the founding report) and PMID 37246732 (Teku, the architecture paper). Both have no PMCID, so routes 2-4 are structurally unavailable, and both Wiley DOIs return HTTP 403 - all five routes in this project's unreadable test fail. Everything this beat says from either paper comes from its abstract, and that is stated in every caveat where it matters.
What this implies for the index fusion, by contrast
This project's partner atlas is organised around the question 'what effector does the partner supply to the retained KMT2A N-terminus?'. In this entity that question has no answer, because there is no retained KMT2A N-terminus and no effector-supplying partner. The census is therefore a boundary marker for the partner model: it shows the model is about 5'-KMT2A fusions in haematopoiesis, and that a completely different set of partners is compatible with KMT2A rearrangement in mesenchyme.
| script | manual enumeration from the primary literature plus PubMed esearch bounds, 2026-09-21 |
|---|---|
| status | run |
| result summary | Recurrent partners YAP1 (dominant) and VIM; single-case CBX6/PYGO1 and LDB1; 16 non-recurrent partners of probable passenger status; zero elongation-machinery partners. |
| source typo | Supplemental Table 2 spells the index gene KTM2A in rows S5 (PHLDB1) and S17 (TMPRSS13). A grep for KMT2A loses two of eighteen cases. |
partners recurrent
{
"YAP1": {
"cases": "16/34 in the screen, 22 in the largest series, plus later case reports",
"kmt2a_contribution": "exons 4/5-6 (CXXC only)",
"class": "Hippo transcriptional co-activator"
},
"VIM": {
"cases": "2/34; 4 published in total",
"kmt2a_contribution": "exon 2 onward (aa 145-3969, SET intact)",
"class": "type III intermediate filament"
}
}partners single case
{
"CBX6 + PYGO1": {
"cases": 1,
"kmt2a_contribution": "not stated in the abstract",
"class": "chromobox / Pygopus"
},
"LDB1": {
"cases": 1,
"kmt2a_contribution": "exons 4-36 (aa 1053-3969, SET intact)",
"class": "LIM domain binding transcriptional adaptor"
}
}non recurrent group
{
"n": 16,
"kmt2a_3prime": 8,
"kmt2a_5prime": 7,
"median_age": 57,
"tp53_mutant_pct": 44,
"verdict": "probable passengers; the source authors call them of unclear significance",
"gap": "CLOSED 2026-09-21. The table was opened: Supplemental Table 2 of PMID 32461620 (41379_2020_582_MOESM2_ESM.xlsx, free, 16 KB). See ana-seven-sarcomas-retain-the-menin-binding-motif-and-three-carry-a-leukaemia-type-fusion.",
"identities": "KMT2A 3-prime (9): MRGPRF ex2, AHNAK ex5, PHLDB1 ex6, GRIK4 ex5, CLIC4 ex1, INTS4 ex19, DIAPH2 ex14, PPP2R1B ex15, UBE4A ex1. KMT2A 5-prime (7): KMT2A ex3::CPT1A, ex8::DOCK10, ex8::C2CD3, ex9::ELP4, ex15::AHDC1, ex20::TMPRSS13, ex22::RALGAPA2.",
"kmt2a_3prime_corrected": 9,
"split_note": "This entry recorded kmt2a_3prime=8 and kmt2a_5prime=7, summing to 15 of 16. The table gives 9 and 7, summing to 16. kmt2a_3prime is left in place above with the correction beside it rather than silently overwritten.",
"kmt2a_5prime_all_retain_mbm": "All 7. Breakpoints at KMT2A exons 3, 8, 8, 9, 15, 20 and 22 are all downstream of exon 1 (aa 1-144, MBM 6-25), and 3 of them (exons 8, 8, 9) fall inside the leukaemic breakpoint cluster region and retain the complete leukaemic N-terminal module including CXXC.",
"verdict_revised": "'Probable passengers' survives as the source authors' own assessment, but the group is no longer functionally opaque, and it is not this entity's least interesting rows: it holds the only KMT2A-rearranged sarcomas that retain the menin-binding motif."
}partner classes present
[ "Hippo transcriptional co-activator", "type III intermediate filament", "chromobox / polycomb reader", "Wnt co-activator (Pygopus)", "LIM domain binding transcriptional adaptor" ]
partner classes absent
[ "super elongation complex subunit (AFF1, AFF4, MLLT1, MLLT3, ELL)", "DOT1L complex member", "P-TEFb component", "PAF1 complex component", "septin" ]
bounded rejection
[ "MLL[tiab] AND sarcoma[tiab] = 61: mostly myeloid sarcoma (extramedullary leukaemia), dropped as a different disease", "Ewing sarcoma menin literature (27888797, 33741715, 32333633, 29672864): read, used only as therapeutic context", "\"sclerosing epithelioid fibrosarcoma\"[tiab] = 222: mostly the conventional MUC4-positive EWSR1/FUS::CREB3L entity; only the 14 KMT2A-mentioning records are on beat", "KMT2A::MAML2 thymoma reviews (38067300, 33674910): read, not used; a different non-haematologic KMT2A entity already in this graph", "soft-tissue pathology update reviews (34958510, 31686193, 38278601): read as maps only", "PRRX1::KMT2D: enumerated and dropped, a different gene with a documented naming hazard" ]
found on topic and unreadable
[ "PMID 31136005 (Yoshida, founding report): no PMCID, routes 2-4 unavailable, Wiley DOI HTTP 403", "PMID 37246732 (Teku, the architecture paper): no PMCID, routes 2-4 unavailable, Wiley DOI HTTP 403" ]
- Counting partners from cohorts assembled by panels that often omit KMT2A gives a distribution biased toward the morphology that prompts testing. Treating YAP1's 47% as the true partner distribution would misstate the entity's composition.
- This census records that no elongation partner has been found, which is a bounded absence over about thirty published cases - a small denominator, and a class of partner nobody in this field is looking for.
- ANSWERED 2026-09-21 -- the table was opened and all 16 are named with exon-level breakpoints; see data.non_recurrent_group.identities and ana-seven-sarcomas-retain-the-menin-binding-motif-and-three-carry-a-leukaemia-type-fusion. The functional classification this question asked for is now possible, and it inverts the group's status: 7 of 16 retain the menin-binding motif and 3 retain the whole leukaemic N-terminal module.
- Has any KMT2A-rearranged sarcoma partner ever appeared as a KMT2A partner in leukaemia? YAP1, VIM, CBX6, PYGO1 and LDB1 are all absent from the leukaemia recombinome as far as this beat checked, and a proper cross-check against that census would be one query.
- Does the entity have an elongation-machinery partner nobody has found yet, or is the absence structural? The former is answerable by re-sequencing archives; the latter would mean mesenchyme cannot tolerate a 5'-KMT2A elongation fusion.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In 34 human KMT2A-fusion-positive sarcomas, YAP1 was the partner in 16 (47%) and VIM in 2, while 16 tumours carried unique non-recurrent partners with KMT2A 3' in eight and 5' in seven, no reciprocal transcripts in any, diverse histologies including leiomyosarcoma, atypical lipomatous tumour, undifferentiated pleomorphic sarcoma and high-grade endometrial stromal sarcoma, a median age of 57 and pathogenic TP53 mutation in 44%.
Pan-sarcoma genomic analysis of KMT2A rearrangements reveals distinct subtypes defined by YAP1-KMT2A-YAP1 and VIM-KMT2A fusions. · Massoth LR, Hung YP, Nardi V, et al. · Mod Pathol 2020What this evidence cannot show
A commercial profiling cohort enriched for advanced disease. The individual identities of the 16 non-recurrent partners are in a supplementary table that was not opened for this entry, so this census lists them as a group rather than by name - a gap a future beat should close, because named partners would let the group be classified functionally.
Evidence that argues against this (1)
- Counting partners in a cohort assembled by a panel that often does not cover KMT2A produces a partner distribution biased toward whatever the panel can see. YAP1's dominance is also inflated by ascertainment, because the SEF-like morphology is what prompts testing in the first place. Warmke LM et al. 2025
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In eight human soft tissue neoplasms with LGFMS/SEF-overlapping morphology lacking MUC4 and EWSR1/FUS-CREB3L fusions, seven carried YAP1-KMT2A fusions and one a PRRX1-KMT2D fusion, with all but one displaying reciprocal gene fusions and gene expression profiles distinct from LGFMS/SEF; separately, one case in a nine-case series showed rearrangement of both KMT2A and MAML2 by FISH.
Recurrent Fusions Between YAP1 and KMT2A in Morphologically Distinct Neoplasms Within the Spectrum of Low-grade Fibromyxoid Sarcoma and Sclerosing Epithelioid Fibrosarcoma. · Puls F, Agaimy A, Flucke U, et al. · Am J Surg Pathol 2020What this evidence cannot show
Eight cases, abstract-level reading, and the PRRX1::KMT2D case involves a different gene whose naming is a documented hazard in this project. The KMT2A/MAML2 double-rearrangement observation comes from a different paper and was by FISH only, which this same literature shows to be unreliable in this entity.
Evidence that argues against this (1)
- The reciprocal fusions reported in all but one case of this series are the basis on which prior authors treated the lesion as a simple reciprocal translocation. The later insertional model rejects that reading, so the same observation supports two incompatible architectures depending on which paper is read. Massoth LR et al. 2020
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Two further VIM::KMT2A-rearranged sarcomas were reported in adult males with the fusion at VIM exon 4 and KMT2A exon 2 in both, described by the authors as confirming an entity with distinct histologic features separable from the YAP1-partnered tumours.
VIM::KMT2A-rearranged sarcomas: A report of two new cases confirming an entity with distinct histologic features. · Almohsen SS, Griffin AM, Dickson BC, et al. · Genes Chromosomes Cancer 2023What this evidence cannot show
Two case reports; with the pan-sarcoma screen's two and the founding report's one, the VIM arm rests on four or five published cases depending on whether the screen's cases overlap other reports. Abstract-level reading.
Evidence that argues against this (1)
- An entity confirmed by four cases with no functional work and no specific immunoprofile is a morphological hypothesis. The authors say so themselves: without molecular testing these tumours are a diagnostic challenge indistinguishable from other monomorphic spindle cell neoplasms. Massoth LR et al. 2020
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
A 47-year-old man's subcutaneous chest spindle cell tumour carried a novel CBX6::KMT2A::PYGO1 fusion gene - a second three-segment arrangement with KMT2A internal - and remained free of recurrence or metastasis 2 years 8 months after surgery without postoperative treatment.
KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1. · Nakamura H, Kukita Y, Wakamatsu T, et al. · Virchows Arch 2023What this evidence cannot show
One case, abstract-level reading, and the authors describe the arrangement as 'highly likely irreproducible'. No KMT2A exon indices are given in the abstract, so this case cannot be placed on the exon map and contributes to the census as a partner name only.
Evidence that argues against this (1)
- CBX6 is a polycomb chromobox and PYGO1 a Wnt co-activator, so this single case adds two partner classes at once on the strength of one tumour. A novel three-part fusion in one patient is as compatible with a private structural accident as with a mechanism. Wang Z et al. 2025
- E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
A novel LDB1::KMT2A fusion involving LDB1 exons 1-10 and KMT2A exons 4-36 was reported in a 19-year-old man's spindle-cell sarcoma, described by the authors as expanding the molecular spectrum of the emerging entity of KMT2A-rearranged sarcomas.
LDB1::KMT2A Fusion in a Spindle-Cell Sarcoma: A Case Report. · Wang Z, Zhang Y, Zhu M, et al. · Genes Chromosomes Cancer 2025What this evidence cannot show
One case with a concurrent pathogenic BCOR frameshift and 5 months of follow-up; abstract-level reading. The phrase 'the emerging entity of KMT2A-rearranged sarcomas' is quoted here as the field's own current characterisation of the entity's status.
Evidence that argues against this (1)
- With a second pathogenic driver present, this case's contribution to a partner census is a partner name rather than an established driver relationship - and the same caution applies to both single-case arrangements in this table. Nakamura H et al. 2023
- E6established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Measured here 2026-09-21 by PubMed esearch: MLL[tiab] AND sarcoma[tiab] returns 61 records of which the majority are myeloid sarcoma (extramedullary acute leukaemia) rather than soft tissue sarcoma, while KMT2A[tiab] AND sarcoma[tiab] returns 55 and "sclerosing epithelioid fibrosarcoma"[tiab] returns 222 of which only 14 mention KMT2A.
PubMed E-utilities esearch, KMT2A-sarcoma partner enumeration and literature bounds · National Center for Biotechnology Information · PubMed E-utilities 2026What this evidence cannot show
Retrieval sizes on 2026-09-21, titles and abstracts only. The 'majority are myeloid sarcoma' judgement comes from reading the returned titles of the KMT2A-scoped set and from the retrieval overlap, not from a case-by-case classification of all 61 MLL records - so it is a characterisation of the contamination, not a count of it.
Evidence that argues against this (1)
- Myeloid sarcoma is dismissed here as a different disease, and that is right as a matter of lineage - but it is a KMT2A-rearranged solid MASS, and the graph already holds pediatric myeloid sarcoma literature. A beat looking for KMT2A-rearranged solid tumours in general should not inherit this beat's exclusion without re-examining it. Massoth LR et al. 2020
full partner enumeration plus the beat's bounded-rejection record
dominant partner, 16 of 34
second recurrent partner, 2 of 34
single-case partner in the census
- related to →KMT2A::MAML2 type B2/B3 thymoma - the same fusion, a different organ, a different disease
read and not used; one sarcoma case had concurrent KMT2A and MAML2 rearrangement by FISH, an unresolved loose end
- analogous to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
not one sarcoma partner is elongation machinery, which is the entire partner class of the index fusion
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
names one of the 16 non-recurrent partners the census recorded as a group because Supplemental Table 2 had not been opened
CLOSES ITS NAMED GAP AND CORRECTS TWO FIGURES: that entry's own open_questions asked what the 16 non-recurrent partners are and recorded that the supplementary table was not opened. It was reachable in one request. The split is 9 with KMT2A 3-prime and 7 with 5-prime, not the 8 and 7 recorded, which summed to 15 of 16; and the group is not functionally opaque -- it holds the only KMT2A-rearranged sarcomas that retain the menin-binding motif.