Renal cell carcinoma (RCC) patients with NF2 driver mutations often present with metastatic disease and have worse survival outcomes, according to research presented at IKCS North America 2022.

Researchers from Memorial Sloan Kettering (MSK) Cancer Center searched the MSK Clinical Sequencing Cohort — which includes data from more than 94,452 patients — for patients with RCC driven by an NF2 mutation.

The cohort included 37 such patients. They had a median age of 64 years, had a median BMI of 25.46 kg/m2, 73.0% were White, 67.5% had metastatic disease at diagnosis, and the median tumor size was 4.7 cm. A total of 14 patients underwent surgery, with 64.29% having cytoreductive surgery and 57.1% having nodal involvement.

Continue Reading

Patients tended to have mutations in the FERM domain of the NF2 coding region. Nearly all patients had copy number loss at chromosome 22 where NF2 is located. Roughly half of patients had copy number loss on chromosome 3, and this may confer a more lethal phenotype of NF2-driven RCC, according to the researchers.

In addition to NF2 driver mutations, patients also had genomic alterations in SETD2 (24%), PBRM1 (19%), BAP1 (16%), ARID1A (8%), ARID2 (8%), TP53 (8%), FAT1 (5%), FH (5%), and KMT2B (5%).

When compared with a cohort of patients with clear cell RCC who did not have NF2 driver mutations (n=641), those with NF2 mutations had inferior overall survival (OS). The median OS was 70.5 months and 28.2 months, respectively (P <.01).

In the NF2 cohort, patients who also had a mutation in 3p genes (such as SETD2, PBRM1, and BAP1) had numerically, but not significantly, inferior OS compared with patients who did not have mutations in 3p genes. The median OS was 16.5 months and 29.6 months, respectively (P =.06).

Disclosures: The study authors did not provide disclosures.


Reese S, Zucker M, Vazquez-Rivera K, et al. NF2-mutant renal cell carcinoma: A comprehensive genomic characterization of an aggressive unclassified renal cell carcinoma. Presented at IKCS North America 2022. November 4-5, 2022. Abstract 44.