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Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma
- Source :
- Oncotarget, Oncotarget, 2015, 6 (22), pp.19279-19289. ⟨10.18632/oncotarget.4220⟩
- Publication Year :
- 2015
- Publisher :
- Impact Journals LLC, 2015.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 6
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.pmid.dedup....8e5799266123d8e27b4141f8c75a2097