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Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling
- Source :
- European urology. 73(1)
- Publication Year :
- 2017
-
Abstract
- Background Papillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for advanced PRCC. Objective To characterize the frequency of genomic alterations (GAs) in patients with advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the context of routine clinical care. Design, setting, and participants Formalin-fixed, paraffin-embedded tissue was obtained for 169 consecutive patients with confirmed PRCC. DNA was extracted and comprehensive genomic profiling was performed in a certified central laboratory. Measurements Hybrid-capture, adaptor ligation-based libraries of up to 315 genes were sequenced to a median coverage of 648×. All classes of GAs were identified, including substitutions, insertions/deletions, copy number alterations, and rearrangements. Results and limitations From 169 patients, either primary tumor tissue (102 patients, 60%) or metastatic tissue (67 patients, 40%) was collected. In patients with type 1 PRCC, commonly altered genes were MET (33%; 8 activating mutations, 5 amplifications at >6 copies), TERT (30%), CDKN2A/B (13%), and EGFR (8%). In patients with type 2 PRCC, commonly altered genes were CDKN2A/B (18%), TERT (18%), NF2 (13%), and FH (13%); MET GAs (5 mutations, 3 amplifications) were observed in 7% of type 2 cases. Notable differences from TCGA data include higher frequencies of MET , NF2 , and CDKN2A/B GAs, association of alterations in SWI/SNF complex genes with type 2 PRCC, and observation of frequent CDKN2A/B alterations in both type 1 and type 2 disease. Conclusions Both the current study and the TCGA experience represent similarly sized cohorts of patients with PRCC. Key differences in GA frequency probably underscore the marked difference in stage distribution between these data sets. These results may inform planned precision medicine trials for metastatic PRCC. Patient summary Papillary renal cell carcinoma (PRCC) is a rare subtype of kidney cancer, and understanding of the biology of advanced PRCC is limited. This report highlights some of the unique biologic features of PRCC that may inform on future use of targeted therapies for the treatment of metastatic disease.
- Subjects :
- 0301 basic medicine
Oncology
Adult
Male
medicine.medical_specialty
Pathology
DNA Copy Number Variations
Urology
Biopsy
Disease
03 medical and health sciences
Young Adult
0302 clinical medicine
CDKN2A
Predictive Value of Tests
Internal medicine
Databases, Genetic
medicine
Biomarkers, Tumor
Humans
Genetic Predisposition to Disease
Gene
Carcinoma, Renal Cell
Aged
Aged, 80 and over
Gene Rearrangement
Papillary renal cell carcinomas
business.industry
Gene Expression Profiling
Gene Amplification
Computational Biology
Genomics
Middle Aged
medicine.disease
Precision medicine
Primary tumor
Kidney Neoplasms
030104 developmental biology
Phenotype
030220 oncology & carcinogenesis
Localized disease
Mutation
Female
business
Transcriptome
Kidney cancer
Subjects
Details
- ISSN :
- 18737560
- Volume :
- 73
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- European urology
- Accession number :
- edsair.doi.dedup.....f127c7a4b72757a5b4079cc7bfe5f564