title: Long interspersed element-1 protein expression is a hallmark of many human cancers.
abstract: Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: nrodic1@jhmi.edu.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Rodić
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland Baltimore County, Baltimore, Maryland.
authors.forename: Reema
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: John
authors.initials: J
authors.lastname: Zampella
authors.affiliation: High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Lixin
authors.initials: L
authors.lastname: Dai
authors.affiliation: High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Taylor
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Duffield
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Montgomery
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lotan
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Westra
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Binder
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Orr
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.affiliation: High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.affiliation: Department of Pediatrics, Robert Wood Johnson Medical School, Rutgers University Cancer Institute of New Jersey, Raymond and Beverly Sackler Foundation, New Brunswick, New Jersey; Cancer Institute of New Jersey, Rutgers University of Medicine and Dentistry, New Brunswick, New Jersey.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Harris
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: kburns@jhmi.edu.
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Burns
mesh_terms: D045744:Cell Line, Tumor; D003850:Deoxyribonuclease I / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D003850:Deoxyribonuclease I; C538849:LINE-1 endonuclease, human