1. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma
- Author
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Bousquet, Guilhem, Bouchtaoui, Morad El, Leboeuf, Christophe, Battistella, Maxime, Varna, Mariana, Ferreira, Irmine, Plassa, Louis-François, Hamdan, Diaddin, Bertheau, Philippe, Feugeas, Jean-Paul, Damotte, Diane, Janin, Anne, Laboratoire de Pathologie (Sorbonne Paris Cité / UNIV Paris Diderot), Université Paris Diderot, Sorbonne Paris Cité, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Grand Hôpital de l'Est Francilien (GHEF), Service de pathologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and leboeuf, Christophe
- Subjects
Male ,human RCC ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,urologic and male genital diseases ,Mice ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,tumor heterogeneity ,metastases human RCC tumor heterogeneity sub-clonal tumor cells TP53 mutation ,Animals ,Humans ,Neoplasm Metastasis ,metastases ,neoplasms ,Carcinoma, Renal Cell ,Aged ,Aged, 80 and over ,TP53 mutation ,Middle Aged ,Genes, p53 ,Xenograft Model Antitumor Assays ,female genital diseases and pregnancy complications ,Kidney Neoplasms ,[SDV] Life Sciences [q-bio] ,Mutation ,Female ,sub-clonal tumor cells ,Tumor Suppressor Protein p53 ,Research Paper - Abstract
International audience; Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53expressing tumor cells and TP53 gene abnormalities. We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived. Using laser-microdissection of p53-expressing tumor cells, we identified TP53mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC.
- Published
- 2015