[en] Cancers of distinct histological subtypes are traditionally thought to arise from different cells of origin. However, alternative models propose that multipotent epithelial progenitors or late-stage transdifferentiation events may give rise to diverse tumor lineages, leaving the pathogenesis of adenosquamous carcinomas unresolved. Given the universal involvement of high-risk human papillomavirus in cervical carcinogenesis, cervical adenosquamous carcinoma offers a unique model to investigate tumor lineage relationships within a shared etiologic context. Here, we integrated histopathological, virological, and genomic analyses of microdissected glandular and squamous components from mixed tumors. Strikingly, both malignant elements displayed identical virological features and shared somatic alterations. Following early lineage separation, the two distinct (pre)cancerous entities evolved independently, exhibiting no component-specific mutational signatures. Taken together, these findings demonstrate that glandular and squamous populations from adenosquamous carcinomas follow independent evolutionary trajectories from a single progenitor cell, providing robust validation in human cancers of the concept of early clonal divergence.
Disciplines :
Oncology
Author, co-author :
Poulain, Florian ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
Malassigné, Victor; Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, 75006 Paris, France, Functional Genomics of Solid Tumors (FunGeST) Laboratory, Équipe Labellisée Ligue Nationale Contre le Cancer, Labex Onco-Immunology, Institut Du Cancer Paris CARPEM, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
RONCARATI, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
Puech, Julien; Laboratory of Virology, Department of Microbiology, Georges Pompidou European Hospital, 75015 Paris, France
Imbeaud, Sandrine; Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, 75006 Paris, France, Functional Genomics of Solid Tumors (FunGeST) Laboratory, Équipe Labellisée Ligue Nationale Contre le Cancer, Labex Onco-Immunology, Institut Du Cancer Paris CARPEM, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
Zucman-Rossi, Jessica; Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, 75006 Paris, France, Functional Genomics of Solid Tumors (FunGeST) Laboratory, Équipe Labellisée Ligue Nationale Contre le Cancer, Labex Onco-Immunology, Institut Du Cancer Paris CARPEM, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
Crum, Christopher P; Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Hubert, Pascale ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Péré, Hélène; Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, 75006 Paris, France, Functional Genomics of Solid Tumors (FunGeST) Laboratory, Équipe Labellisée Ligue Nationale Contre le Cancer, Labex Onco-Immunology, Institut Du Cancer Paris CARPEM, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France, Laboratory of Virology, Department of Microbiology, Georges Pompidou European Hospital, 75015 Paris, France
Veyer, David; Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, INSERM, 75006 Paris, France, Functional Genomics of Solid Tumors (FunGeST) Laboratory, Équipe Labellisée Ligue Nationale Contre le Cancer, Labex Onco-Immunology, Institut Du Cancer Paris CARPEM, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France, Laboratory of Virology, Department of Microbiology, Georges Pompidou European Hospital, 75015 Paris, France
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
English
Title :
Clonal origin and early lineage divergence in adenosquamous carcinoma.
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