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Updated: Jul 11, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Tumor necrosis factor-alpha gene mutations and genotype changes in renal cell carcinoma
K Nakajima1, M Sasaki, D Nojima
1Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, USA.
Purpose:
We tested the hypothesis that genotype changes in the promoter region of tumor necrosis factor-alpha and exon 1 are associated with renal cell carcinoma.
Materials And Methods:
We analyzed genotypic changes at the 3 polymorphic loci of tumor necrosis factor-alpha -238, -308 and 488 using tumor and normal tissues from 81 Japanese patients with renal cell carcinoma.
Results:
Of the 81 patients 14 (17%) had point mutations from G to A, including 8 (57%) with point mutations at multiple loci. Six of the 8 patients (75%) with point mutations at multiple loci were classified with stage 4 renal cell carcinoma. Of the 81 patients 14 were classified with stage 4 carcinoma, including 9 (64%) with point mutation from G to A. Normal tissue from cancer patients showed an increased frequency of the GA genotype at loci -238 and 488 compared to healthy controls (37% versus 9% and 30% versus 12%, respectively). The relative risk of renal cell carcinoma was 6.5-fold higher in patients with the GA genotype at locus -238 (p <0.001) and 2.9-fold higher in those with the GA genotype at locus 488 (0.01 < p <0.025) when comparing normal tissue from renal cell carcinoma patients with that of healthy controls.
Conclusions:
Point mutation from G to A, and the GA genotype at loci -238 and 488 of the TNF-alpha gene were common in patients with advanced renal cell carcinoma. The genotype change at loci -238 and 488 of the TNF-alpha gene are associated with renal cancer pathogenesis.
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