ArticleMolecular oncology2026
Intrapatient tumour heterogeneity and clonal evolution in an autopsy study of metastatic salivary gland cancer.
Article in Molecular oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Genetic tumour heterogeneity, driven by clonal evolution, contributes to therapy resistance in many cancers. Most salivary gland cancers, including adenoid cystic carcinoma (AdCC) and myoepithelial carcinoma (MECA), lack effective systemic treatments, highlighting the need to characterise their evolutionary profiles. In this autopsy study, we reconstructed genetic heterogeneity and clonal evolution in two patients with metastatic AdCC and one patient with metastatic MECA. Radiology-guided autopsy was performed between 12 and 56 h after out-of-hospital death. One hundred forty-nine tumour samples were snap-frozen, of which 17 (4-7 per patient) were selected for whole-genome sequencing. Phylogenetic reconstruction was performed using CONIPHER. Autopsy revealed multiple metastatic sites not visible on antemortem or postmortem imaging. MYB-NFIB gene fusions were present across all tumour sites from the two AdCC patients, while a LIFR-PLAG1 fusion was detected in all samples from the MECA patient. All three cases showed extensive genetic tumour heterogeneity and branched phylogenies, suggestive of parallel evolution. Histologic growth patterns were consistent across metastatic sites. Overall, this study demonstrated marked genetic heterogeneity and branched evolution in these AdCC and MECA patients.
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