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Title: Identification of Targetable FGFR Gene Fusions in Diverse Cancers      
Identifier:
phs000602.v1.p1
description:
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.
accesstypes:
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enclave
landingpage: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000602.v1.p1
authentication: simpleLogin
none
authorization:
none
duaIndividual
name:
Neoplasms
Cholangiocarcinoma
Breast Neoplasms
Prostatic Neoplasms
Urinary Bladder Neoplasms
Mouth Neoplasms
affiliations:
University of Michigan, MI, USA
name:
Arul M. Chinnaiyan, MD, PhD
roles:
Principal Investigator
affiliations:
National Institutes of Health, Bethesda, MD, USA
name:
U01 CA111275
roles:
University of Michigan
performedBy:
TitleNameInstitute Principal InvestigatorArul M. Chinnaiyan, MD, PhDUniversity of Michigan, MI, USA University of MichiganU01 CA111275National Institutes of Health, Bethesda, MD, USA
downloadURL: https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=DUC&view_pdf&stacc=phs000602.v1.p1
Identifier:
phs000602.v1.p1_policy
name:
Data Use Certificate
Identifier:
1
name:
Disease-specific-Cancer
alternateIdentifiers:
yes
selectionCriteria:

5.0 ELIGIBILITY

5.1 Patient population

This protocol is designed to collect biospecimens with annotated clinical data from patients with advanced or refractory cancer.

5.2 Inclusion Criteria: (Must satisfy all criteria and either #3 or #4)

  1. A histologically or cytologically confirmed diagnosis of cancer.
  2. Patients with any advanced or refractory malignancy.
  3. Patients are undergoing standard of care surgeries or procedures where specimens will be first used for routine pathologic assessment and only then will leftover tissue be used for research purposes.
  4. OR
  5. Patients must have tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and patients are medically fit to undergo a tissue biopsy or surgical procedure to get tumor tissue OR if patients do not have a tumor suitable for biopsy but have another tissue available for molecular evaluation.
  6. Older than or equal to 18 years of age.
  7. Procedure-specific signed informed consent prior to initiation of any study-related procedures.
  8. Women and minorities are included in this protocol.
  9. Patients with multiple malignancies remain eligible.
  10. Patients with an inherited cancer syndrome or a medical history suggestive of an inherited cancer syndrome remain eligible.

5.3 Exclusion Criteria:

  1. It is the enrolling study physician's discretion to decide if a patient is not fit enough to undergo tissue biopsy.
  2. Patients who are incarcerated are not eligible to participate.
  3. Women who are pregnant.

5.4 Women of childbearing age.

For women of childbearing age, there are no screening requirements. We note that most patients entering this study are seeking eligibility for therapy or other clinical trial, in which case they are generally asked to avoiding becoming pregnant and even exercise some form of contraception by their medical oncologist. For women of childbearing age, their referring medical oncologist will discuss necessity or role for appropriate contraception. This is not part of the study activity, nor is it required for participation.

types:
Case Set
dateReleased:
02-28-2013
version:
phs000602.v1.p1
dateModified:
02-28-2013
abbreviation:
NCI
name:
NCI
ID:
0
name:
dbGaP

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