Renal Cell Carcinoma with Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

Sean R. Williamson, David J. Grignon, Liang Cheng, Laura Favazza, Dibson D. Gondim, Shannon Carskadon, Nilesh S. Gupta, Dhananjay A. Chitale, Shanker Kalyana-Sundaram, Nallasivam Palanisamy

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26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)287-298
Number of pages12
JournalAmerican Journal of Surgical Pathology
Volume41
Issue number3
DOIs
StatePublished - Jan 1 2017

Keywords

  • TFEB gene
  • chromosome 6p
  • kidney cancer
  • renal cell carcinoma
  • tumor classification

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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    Williamson, S. R., Grignon, D. J., Cheng, L., Favazza, L., Gondim, D. D., Carskadon, S., Gupta, N. S., Chitale, D. A., Kalyana-Sundaram, S., & Palanisamy, N. (2017). Renal Cell Carcinoma with Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis? American Journal of Surgical Pathology, 41(3), 287-298. https://doi.org/10.1097/PAS.0000000000000776