Metastatic clear-cell renal cell carcinoma: a frequent NOTCH1 mutation predictive of response to anti-NOTCH1 CB-103 treatment.

ABSTRACT:

Background

Clear-cell renal cell carcinomas (ccRCCs) are malignant tumors with high metastatic potential and resistance to treatments occurs almost constantly. Compared to primary tumors, there are still limited genomic data that has been obtained from metastatic samples.

Methods

We aimed to characterize metastatic ccRCC by way of whole-genome analyses of metastatic formalin-fixed samples, using OncoScan^® technology. We identified a frequent, unexpected pL1575P NOTCH1 mutation which we set out to characterize for translational purposes. We thus implemented patient-derived xenografts from metastatic samples of human ccRCC to explore its clinical significance.

Results

We showed that pL1575P NOTCH1 mutation was an activating mutation, leading to the expression

SUBMITTER: Bui TO 

PROVIDER: S-EPMC10184347 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature