title: FGFR3-TACC3: A novel gene fusion in cervical cancer.
abstract: Cervical cancer epitomizes the success of cancer prevention through the human papillomavirus (HPV) vaccine, but significant challenges remain in the treatment of advanced disease. We report the first three cases of cervical carcinoma harboring an FGFR3-TACC3 fusion, which serves as a novel therapeutic target. The fusion, identified by comprehensive genomic profiling, activates the FGFR pathway that has been implicated in HPV-driven carcinogenesis. One of the patients whose tumor contained the FGFR3-TACC3 fusion was treated with an investigational FGFR tyrosine kinase inhibitor. Concomitant molecular alterations involving the PI3K/AKT/mTOR and RAF/MEK pathways were also identified and suggest other treatment strategies that deserve investigation. This case series highlights the role of comprehensive genomic profiling in the identification of new therapeutic targets and in targeted therapy selection for patients with cervical cancer.
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University 645 N Michigan Ave Suite 1006 Chicago, IL, 60611, Unites States.
authors.forename: Benedito A
authors.initials: BA
authors.lastname: Carneiro
authors.affiliation: Foundation Medicine, Inc., 150 Second Street, 1st Floor, Cambridge, MA 02141, United States.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, 251 East Huron St., Galter Suite 3-150, Chicago, IL 60611, United States.
authors.forename: Suneel D
authors.initials: SD
authors.lastname: Kamath
authors.affiliation: Foundation Medicine, Inc., 150 Second Street, 1st Floor, Cambridge, MA 02141, United States.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Ward Building Room 3-140, Chicago, IL 60611, United States.
authors.forename: Ajit S
authors.initials: AS
authors.lastname: Paintal
authors.affiliation: Texas Oncology-McAllen, 1901 South 2nd Street, McAllen, TX 78503, United States.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Restrepo
authors.affiliation: Division of Gynecology Oncology, Northwestern University Feinberg School of Medicine, 250 E Superior St., NMH/Prentice Women's Hospital Room 5-2168, Chicago, IL 60611, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Berry
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University 645 N Michigan Ave Suite 1006 Chicago, IL, 60611, Unites States.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University 645 N Michigan Ave Suite 1006 Chicago, IL, 60611, Unites States.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Johnson
keywords: Adenocarcinoma of the cervix; Cervical carcinoma; FGFR inhibitors; FGFR translocations; FGFR-TACC3; Targeted therapy