Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene
Autor: | Sean R. Williamson, Liang Cheng, Laura Favazza, Dibson Gondim, Dhananjay Chitale, David J. Grignon, Nilesh S. Gupta, Shannon Carskadon, Nallasivam Palanisamy, Shanker Kalyana-Sundaram |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty Chromosomal translocation Biology Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Gene duplication Biomarkers Tumor medicine Humans SMARCB1 Carcinoma Renal Cell In Situ Hybridization Fluorescence Aged Neoplasm Staging Chromosome 7 (human) medicine.diagnostic_test Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Gene Amplification Chromosome Middle Aged Immunohistochemistry Kidney Neoplasms Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Cancer research TFEB Chromosomes Human Pair 6 Female Surgery Anatomy Clear cell Fluorescence in situ hybridization |
Zdroj: | American Journal of Surgical Pathology. 41:287-298 |
ISSN: | 0147-5185 |
Popis: | Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics. |
Databáze: | OpenAIRE |
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