Loss of heterozygosity of key tumor suppressor genes in advanced renal cancer patients treated with nivolumab

Immunotherapy. 2018 Jul;10(9):743-752. doi: 10.2217/imt-2017-0160.

Abstract

Aim: We studied the possible clinical significance of loss of heterozygosity (LOH) at key tumor suppressor genes loci in advanced renal cancer patients treated with nivolumab.

Methods: LOH study was performed on 3p14.2 (FHIT gene); 3p21.3-21.2; 9p21 (BDMF gene); 9p22 (SH3GL2 gene).

Results: Of 12 patients, 8 (67%) had LOH. The most affected gene was FHIT. All five patients with LOH at FHIT locus had good outcome, mean progression free survival of 6.8 months. The patients LOH negative at FHIT locus had mean progression free survival of 4 months, 67% were treatment refractory. Overall, 75% of patients with LOH of at least one gene had benefit; 75% of LOH negative cases were refractory.

Conclusion: LOH at key tumor suppressor genes should be further investigated as predictive for immunotherapy.

Keywords: FHIT; loss of heterozygosity; renal cell carcinoma.

MeSH terms

  • Acid Anhydride Hydrolases / genetics*
  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / diet therapy*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / mortality
  • DNA Repair / genetics
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / mortality
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Nivolumab / therapeutic use*
  • Pilot Projects
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Neoplasm Proteins
  • SH3GL2 protein, human
  • Tumor Suppressor Proteins
  • fragile histidine triad protein
  • Nivolumab
  • Acid Anhydride Hydrolases