BMP4
Overview
BMP4 (Bone Morphogenetic Protein 4) is a secreted ligand of the TGF-beta superfamily that plays critical roles in embryonic development, cell differentiation, and tissue patterning. BMP4 signals through SMAD transcription factors to regulate developmental processes including neural-crest specification, kidney morphogenesis, and osteogenesis. In the cancer genomics corpus, BMP4 has been identified as a marker of transcriptional sub-group identity in malignant rhabdoid tumors (MRT), where its differential expression reflects underlying developmental heterogeneity.
Alterations observed in the corpus
- BMP4 is among the most over-expressed genes in mRNA sub-group 1 (alongside DLK1 and MEOX2) of extra-cranial malignant rhabdoid tumors (MRT); sub-group 1 (BMP-signaling/differentiation-enriched) was enriched for extra-renal sites and was more AT/RT-like (10/11 AT/RT-up genes shared) in an NMF analysis of 40 MRT RNA-Seq cases PMID:26977886
Cancer types (linked)
- MRT / MRTL: BMP4 over-expression marks mRNA sub-group 1 of extra-cranial MRT; this sub-group is enriched for extra-renal cases and resembles the AT/RT-like transcriptional subtype described by prior AT/RT studies. BMP4 expression is not altered by mutation but reflects downstream transcriptional reprogramming following SMARCB1 loss. PMID:26977886
Co-occurrence and mutual exclusivity
- BMP4 over-expression (sub-group 1) is associated with extra-renal tumor site (Fisher’s exact P = 0.04 for sub-group 1 enrichment in extra-renal cases) and with an AT/RT-like transcriptional profile. Sub-group 2 (over-expressing WNT5A, PCDH18, TCF21, MEIS1) is mutually exclusive with sub-group 1 by NMF assignment. PMID:26977886
Therapeutic relevance
- No direct therapeutic targeting of BMP4 is described in the corpus; the BMP4/sub-group-1 axis is hypothesis-generating for BMP-pathway inhibition in a subset of MRT but no drug or clinical outcomes data are reported. PMID:26977886
Open questions
- Whether BMP4 over-expression is a functional dependency in sub-group 1 MRT or a passenger of developmental state is not established; the mechanistic link between SMARCB1 loss and BMP4 upregulation is not resolved. PMID:26977886
Sources
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