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Overrepresentation of 7q31 and 17q in renal cell carcinomas
L Glukhova1, A F Goguel, I Chudoba
1Laboratoire de Cytogénétique et Génétique Oncologiques, Institut Gustave Roussy, Villejuif, France.
Abstract:
Xenografts from four metastatic renal cell carcinomas (RCCs) were established in immunodeficient mice. All tumors exhibited cytogenetic features specific for the papillary subtype, namely, partial or total polysomy of chromosomes 7 and 17 and integrity of 3p. Cytogenetic analysis of the initial and xenografted tumors indicated that although clonal characteristics were consistently maintained in xenografts derived from metastases, a minor clone had been selected for in the xenografts derived from the primary tumors. Reverse painting and comparative genomic hybridization (CGH) allowed us to localize minimal overrepresented genomic regions to 7q31, where the MET protooncogene is located, and to 17q. Other overrepresented regions were 8q in all xenografts and Xq22-qter in three of them. The gain of genetic material from these regions may be a key factor ensuring the papillary nature of RCCs and their survival in xenografts.
Insights
This study investigated renal cell carcinoma (RCC) xenografts, revealing specific chromosomal gains in papillary RCC subtypes. These genetic alterations may drive tumor characteristics and survival in xenograft models.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Renal cell carcinoma (RCC) is a heterogeneous malignancy.
- Papillary RCC (PRCC) subtypes exhibit distinct cytogenetic profiles.
- Understanding genetic alterations in PRCC is crucial for targeted therapies.
Purpose of the Study:
- To characterize the cytogenetic features of papillary renal cell carcinoma (PRCC) xenografts.
- To identify genetic alterations associated with PRCC subtype and xenograft survival.
- To investigate clonal evolution in primary versus metastatic RCC xenografts.
Main Methods:
- Establishment of xenografts from four metastatic renal cell carcinomas (RCCs) in immunodeficient mice.
- Cytogenetic analysis, including reverse painting and comparative genomic hybridization (CGH).
- Analysis of clonal characteristics in primary and metastatic tumor xenografts.
Main Results:
- All xenografts displayed cytogenetic features of papillary RCC, including polysomy of chromosomes 7 and 17.
- Consistent clonal characteristics were maintained in xenografts from metastases, with minor clone selection in primary tumor xenografts.
- Overrepresented genomic regions identified at 7q31 (MET protooncogene locus), 17q, 8q, and Xq22-qter.
Conclusions:
- Genetic gains in specific chromosomal regions (7q31, 17q, 8q, Xq) are associated with the papillary phenotype of RCC.
- These genetic alterations likely contribute to the survival and characteristics of PRCC in xenograft models.
- Xenografts serve as valuable models for studying PRCC clonal evolution and genetic drivers.