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Understanding the genomic underpinnings of metastatic chromophobe renal cell carcinoma
- Source :
- Journal of Clinical Oncology. 34:513-513
- Publication Year :
- 2016
- Publisher :
- American Society of Clinical Oncology (ASCO), 2016.
-
Abstract
- 513 Background: Chromophobe renal cell carcinoma (chRCC) is the third most common histologic subtype of kidney cancer. While most of these tumors have an indolent behavior, 7% of patients with chRCC develop metastases, with no currently available standard of care. The Cancer Genome Atlas characterized chRCC, highlighting pathognomonic single copy chromosomal losses of 1, 2, 6, 10, 13 and 17, as well as a minimal mutation burden distinguishing it from all other cancer types. However, only 15% of the analyzed patients had advanced disease. We analyzed metastatic chRCC to further characterize these tumors and elucidate mechanisms leading to aggressive disease using a variety of next generation and whole genome sequencing. Methods: Our cohort of metastatic chRCC consisted of 40 patients with available clinical and pathologic data. Whole genome sequencing (WGS) was performed on 6 patients (4 primary tumors and 2 metastases), 42 additional samples from 33 patients were analyzed using targeted next-generation sequencing (MSK-IMPACT). Notably, we were able to collect and analyze matched primary and metastatic tumors from 7 patients. As control cohort 27 non-metastatic chRCC tumors were sequenced with MSK-IMPACT. Copy number patterns were computed with OncoSNP seq and FACETS. Results: The most commonly mutated genes in the aggressive chRCC tumors were TP53 and PTEN (WGS: TP53 67 %, PTEN 33%; MSK-IMPACT: TP53 61%, PTEN 27%). No other genes were mutated frequently. Primary tumor samples of chRCC did show the typical pattern of chromosomal losses in 1, 2, 6, 10, 13 and 17. Interestingly, these canonical losses could not be detected in the metastases even when accounting for tumor purity. Conclusions: TP53 and PTEN mutations are highly enriched in both primary and metastatic tumors of aggressive chRCC compared to the non-aggressive tumors and likely play a critical role in disease progression. More intriguingly, the observation of differential copy numbers in matched primary and metastatic tumors suggest whole genome or whole chromosome events in these samples. We are currently employing different bioinformatic and cytogenetic platforms to validate our novel hypothesis of chromosomal events as driver for metastatic development in chRCC.
- Subjects :
- Whole genome sequencing
Cancer Research
Pathology
medicine.medical_specialty
Standard of care
business.industry
Chromophobe Renal Cell Carcinoma
030232 urology & nephrology
Aggressive disease
Single copy
medicine.disease
03 medical and health sciences
0302 clinical medicine
Oncology
Pathognomonic
030220 oncology & carcinogenesis
Advanced disease
Medicine
business
Kidney cancer
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi...........354469b2a504ead0a7eaf4b92af75ab4