TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management
| Autor: | William R. Sukov, Brian A. Costello, Sounak Gupta, Jeannette G Rustin, Binu Porath, Bradley C. Leibovich, George Vasmatzis, Sarah H. Johnson, John C. Cheville, R. Houston Thompson, Priya Rao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Vascular Endothelial Growth Factor A medicine.medical_specialty Pathology DNA Copy Number Variations medicine.medical_treatment Biology Polymorphism Single Nucleotide Pathology and Forensic Medicine Metastasis Targeted therapy 03 medical and health sciences 0302 clinical medicine Renal cell carcinoma Gene duplication Carcinoma medicine Humans Carcinoma Renal Cell Aged Aged 80 and over Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Gene Amplification Middle Aged medicine.disease Nephrectomy Kidney Neoplasms 030104 developmental biology 030220 oncology & carcinogenesis TFEB Female Hematopathology |
| Zdroj: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 30(7) |
| ISSN: | 1530-0285 |
| Popis: | A subset of renal cell carcinomas shows TFEB overexpression secondary to MALAT1-TFEB gene fusion. As alternate mechanisms of TFEB overexpression are likely to have the same effect, we sought to determine the frequency of amplification of TFEB and the adjacent VEGFA gene at 6p21.1. As patients with metastatic renal cell carcinomas are managed with anti-VEGF therapies, we retrospectively assessed therapeutic response in patients with amplified tumors. Amplification status was analyzed for 875 renal cell carcinomas from our institution, a consultative case and 794 cases from The Cancer Genome Atlas. Cases were classified as having low level (5-10 copies), and high-level amplification (>10 copies), and were further analyzed for adjacent oncogene copy number status (n=6; 3 single-nucleotide polymorphism genomic microarray, 3 The Cancer Genome Atlas) and structural rearrangements (n=1; mate-pair sequencing). These were then reviewed for histopathology, immunophenotype, and response to VEGF-targeted therapy on follow-up. In all, 10/875 (1.1%) institutional cases, 1 consultative case, and 3/794 (0.4%) of The Cancer Genome Atlas cases showed TFEB high-level amplification, while 14/875 (1.6%) cases showed TFEB low-level amplification. All cases had associated VEGFA amplification. This was confirmed with evaluation for copy number changes (n=6). The 6p21.1 high and low-level amplified tumors occurred in adults (mean age: 66), with over half being ≥pT3 (13/25, 52%), and most showed oncocytic, tubulopapillary features and high grade (≥grade 3: 20/22, 91%). These were aggressive tumors with metastasis and death from renal cell carcinoma in 11 (of 24, 46%) cases. Four patients received targeted therapy and had a mean survival of 31 months (range: 17-50) post nephrectomy. In summary, a group of aggressive renal cell carcinomas show genomic amplification of the 6p21.1 region including TFEB and VEGFA genes and share morphologic features. Additional studies are warranted to determine whether these patients respond to anti-VEGF therapy. |
| Databáze: | OpenAIRE |
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