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.^[1]

IHC Markers

Positive: CD10 , CD117, E-cadherin, EMA, CK7, PAX8, PAX2, AMACR.

Negative: vimentin, RCC, CA-IX.

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%)^[2]

Mutations (SNV/INDEL)

From Cosmic Mutated in >20%^[3]

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^[4]

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

↑ Diaz JI, Mora LB, Hakam A. The Mainz Classification of Renal Cell Tumors. Cancer Control. 1999 Nov;6(6):571-579
↑ 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.
↑ COSMIC (http://cancer.sanger.ac.uk/cosmic)
↑ 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.

[1] Diaz JI, Mora LB, Hakam A. The Mainz Classification of Renal Cell Tumors. Cancer Control. 1999 Nov;6(6):571-579

[davis-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] COSMIC (http://cancer.sanger.ac.uk/cosmic)

[4] 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.

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