Dataset Information

Proteogenomic landscape of clear cell renal cell carcinoma response to tyrosine kinase inhibitor

ABSTRACT: We performed proteomic analysis of 115 ccRCC patients samples undergoing sunitinib treatment.

ORGANISM(S): Homo Sapiens

SUBMITTER: Chen Ding

PROVIDER: PXD042844 | iProX | Thu Jun 08 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Publications

Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor.

Zhang Hailiang H Bai Lin L Wu Xin-Qiang XQ Tian Xi X Feng Jinwen J Wu Xiaohui X Shi Guo-Hai GH Pei Xiaoru X Lyu Jiacheng J Yang Guojian G Liu Yang Y Xu Wenhao W Anwaier Aihetaimujiang A Zhu Yu Y Cao Da-Long DL Xu Fujiang F Wang Yue Y Gan Hua-Lei HL Sun Meng-Hong MH Zhao Jian-Yuan JY Qu Yuanyuan Y Ye Dingwei D Ding Chen C

Nature communications 20230717 1

The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristoloch ...[more]

PMID: 37460463

Similar Datasets

Project description:Background:Acquired resistance to targeted drugs is largely due to intra-tumor molecular heterogeneity and clonal selection. Objective:The objective of this study was to determine molecular alterations and mediating resistant mechanisms and to suggest additional treatment options.Design, Setting, and Participants:Four patients were enrolled into the MORE (Molecular Renal Cancer Evolution) trial. We investigated the mutational spectra of metastatic clear cell renal cell carcinoma (ccRCC) at baseline and compared them to those upon clonal evolution at progression on systemic therapy with tyrosine kinase inhibitors.Outcome Measurements:DNA was isolated from tumor tissues after surgery, metastasis biopsies after progression on sunitinib or axitinib, and subjected to whole-exome sequencing (WES). In addition, the exomes of circulating tumor DNA (ctDNA) from two patients were sequenced at baseline and at progression.Results and Limitations:Our data provide evidence for clonal evolution and various acquired resistance mechanisms of ccRCC with subclonal mutations in FLT4, MTOR, ITGA3/5, SETD2, and VHL on metastatic progression. The limited number of shared mutations in tissue and plasma biopsies indicates that both sources provide complementary information, possibly due to mutations present in metastatic lesions which were not amenable to tissue sampling but are represented in the ctDNA. Conclusion:Acquired resistance to targeted therapies in metastatic ccRCC is due to intra-tumor heterogeneity and clonal evolution. Larger patient cohorts have to be studied to estimate the benefit of WES from biopsies and ctDNA for therapy decision in metastatic ccRCC.Patient Summary:We analyzed the molecular profiles of ccRCC patients in primary tissues and metastatic tissues upon progression on tyrosine kinase inhibitor therapy. Clinically relevant mutations upon progression were detected in the metastatic sites of all of four patients, suggesting that it might be possible to derive therapies based on sequencing the metastases.?HIPO-045

Dataset Information

Proteogenomic landscape of clear cell renal cell carcinoma response to tyrosine kinase inhibitor

Publications

Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure