ID
45386
Beskrivning
Principal Investigator: Arul M. Chinnaiyan, MD, PhD, University of Michigan, MI, USA MeSH: Neoplasms,Cholangiocarcinoma,Breast Neoplasms,Prostatic Neoplasms,Urinary Bladder Neoplasms,Mouth Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000602 In this study, patients with advanced cancer across all histologies were enrolled in our IRB approved clinical sequencing program, called MI-ONCOSEQ, to go through an integrative sequencing which includes whole exome sequencing of the tumor and matched normal, and transcriptome sequencing. Four index cases were identified which harbor gene rearrangements of FGFR2 including two cholangiocarcinoma cases, a metastatic breast cancer case, and a metastatic prostate cancer case. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, including TCGA, we identified FGFR gene fusions with intact kinase domains of FGFR1, FGFR2, or FGFR3 in cholangiocarcinoma, breast cancer, prostate cancer, lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins in vitro induced cell proliferation, and bladder cancer cell lines that harbors FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Due to the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts which incorporate transcriptome analysis for gene fusions are poised to identify rare, targetable FGFR fusions across diverse cancer types.
Länk
Nyckelord
Versioner (1)
- 2022-11-11 2022-11-11 - Simon Heim
Rättsinnehavare
Arul M. Chinnaiyan, MD, PhD, University of Michigan, MI, USA
Uppladdad den
11 november 2022
DOI
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Licens
Creative Commons BY 4.0
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dbGaP phs000602 Identification of Targetable FGFR Gene Fusions in Diverse Cancers
Subject ID, consent group, subject source, subject source ID, affection status of patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, subject source ID, affection status of patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
- Subject ID, sample ID, sample source, sample source ID, and sample use of samples obtained from patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
- Sample ID, body site where sample was obtained, analyte type, tumor status of sample, cell line status, alias name of sample obtained from patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
Similar models
Subject ID, consent group, subject source, subject source ID, affection status of patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, subject source ID, affection status of patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
- Subject ID, sample ID, sample source, sample source ID, and sample use of samples obtained from patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
- Sample ID, body site where sample was obtained, analyte type, tumor status of sample, cell line status, alias name of sample obtained from patients with advanced cancer of different localizations and involved in the "Identification of Targetable FGFR Gene Fusions in Diverse Cancers" project.
C1257890 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,2])
C0681850 (UMLS CUI [1,3])
C3847505 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,3])