PBRM1 is thought to be a
tumor suppressor gene in many cancer subtypes largely due to the mutational pattern. Most notably, mutations and copy number alterations in
PBRM1 are highly prevalent in
clear cell renal cell carcinoma (ccRCC).
Role in renal carcinoma Loss of function mutations in
PBRM1 often co-occur with loss of function mutations in the
VHL gene in
clear cell renal cell carcinoma (ccRCC). The inactivation of PBRM1 in combination with biallelic loss of VHL has been shown to potentiate
HIF1α signaling and activate the pro-tumorigenic NF-κB pathway. Genetic loss of
PBRM1 is thought to underlie the early initiation of ccRCC due to the sufficiency of conditional deletion of
Pbrm1 and
Vhl for renal carcinomagenesis in mice. While several studies have identified a favorable outcomes among advanced ccRCC cases with
PBRM1 mutations when treated with
immune checkpoint inhibitors, there is still debate about the utility of
PBRM1 status as a biomarker for response to ICI therapy. == References ==