Chromophobe renal cell carcinoma
Contributors
Daynna Wolff, PhD FACMG
Yajuan Liu, PhD
Rajyasree Emmadi, MD
Banumathy Gowrishankar, PhD
Jane Houldsworth, PhD
Tumor Type
Renal Cell Carcinoma
Tumor Classification
Chromophobe Renal Cell Carcinoma
Description
Chromophobe Renal Cell Carcinoma derives from the intercalated cells of the collecting duct epithelium and accounts for ~5% of renal tumors (Diaz JI, Mora LB, Hakam A. The Mainz Classification of Renal Cell Tumors. Cancer Control. 1999 Nov;6(6):571-579).
IHC Markers
Positive: CD10 , CD117, E-cadherin, EMA, CK7, PAX8, PAX2, AMACR.
Genomic Gain/Loss/LOH
| Chromosome | Gain/Loss/Amp | Region |
|---|---|---|
| 1 | Loss | Chr1 (90%) |
| 2 | Loss | Chr2 (80%) |
| 3 | Loss | Chr3 (25%) |
| 5 | Loss | Chr5 (20%) |
| 6 | Loss | Chr6 (90%) |
| 8 | Loss | Chr8 (15%) |
| 9 | Loss | Chr9 (25%) |
| 10 | Loss | Chr10 (90%) |
| 11 | Loss | Chr11 (10%) |
| 13 | Loss | Chr13 (85%) |
| 17 | Loss | Chr17 (90%) |
| 18 | Loss | Chr18 (15%) |
| 21 | Loss | Chr21 (70%) |
Rearrangements
TERT (upstream) (5p15) (12%)
Mutations (SNV/INDEL)
From Cosmic Mutated in >20%
Mutated in 10-20%
Mutated in 5-10%
Mutated in 2-5%
KMT2D, KMT2C, TERT, MET, ARID1A, FAAH2, PDHB, PDXDC1, ZNF765
mtDNA
Epigenomics (methylation)
epigenetic silencing of CDKN2A
Main Pathways Involved
MTOR pathway targeted (23% cases), increased expression of genes involved in oxidative phosphorylation
Diagnosis
Overall loss of whole chormosomes, in particular of chromosomes 1, 2, 6, 10, 13, 17, and 21, eosinophilic variant is mostly diploid
Prognosis
Overall low risk of tumor progression, metastasis, and disease-specific death
Therapeutics
Familial Forms
Birt-Hogg-Dube syndrome (BHD): FLCN (17p11.2)
Links
References
1. Speicher MR, Schoell B, du Manoir S, Schröck E, Ried T, Cremer T, Störkel S, Kovacs A, Kovacs G. Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am J Pathol. 1994 Aug;145(2):356-64.
2. Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, Buhay C, Kang H, Kim SC, Fahey CC, Hacker KE, Bhanot G, Gordenin DA, Chu A, Gunaratne PH, Biehl M, Seth S, Kaipparettu BA, Bristow CA, Donehower LA, Wallen EM, Smith AB, Tickoo SK, Tamboli P, Reuter V, Schmidt LS, Hsieh JJ, Choueiri TK, Hakimi AA; Cancer Genome Atlas Research Network, Chin L, Meyerson M, Kucherlapati R, Park WY, Robertson AG, Laird PW, Henske EP, Kwiatkowski DJ, Park PJ, Morgan M, Shuch B, Muzny D, Wheeler DA, Linehan WM, Gibbs RA, Rathmell WK, Creighton CJ. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014 Sep 8;26(3):319-30.
3. Durinck S, Stawiski EW, Pavía-Jiménez A, Modrusan Z, Kapur P, Jaiswal BS, Zhang N, Toffessi-Tcheuyap V, Nguyen TT, Pahuja KB, Chen YJ, Saleem S, Chaudhuri S, Heldens S, Jackson M, Peña-Llopis S, Guillory J, Toy K, Ha C, Harris CJ, Holloman E, Hill HM, Stinson J, Rivers CS, Janakiraman V, Wang W, Kinch LN, Grishin NV, Haverty PM, Chow B, Gehring JS, Reeder J, Pau G, Wu TD, Margulis V, Lotan Y, Sagalowsky A, Pedrosa I, de Sauvage FJ, Brugarolas J, Seshagiri S. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet. 2015 Jan;47(1):13-21.