Long interspersed element-1 protein expression is a hallmark of many human cancers

Nemanja Rodić; Reema Sharma; Rajni Sharma; John Zampella; Lixin Dai; Martin S Taylor; Ralph H Hruban; Christine A Iacobuzio-Donahue; Anirban Maitra; Michael S Torbenson; Michael Goggins; Ie-Ming Shih; Amy S Duffield; Elizabeth A Montgomery; Edward Gabrielson; George J Netto; Tamara L Lotan; Angelo M De Marzo; William Westra; Zev A Binder; Brent A Orr; Gary L Gallia; Charles G Eberhart; Jef D Boeke; Chris R Harris; Kathleen H Burns

doi:10.1016/j.ajpath.2014.01.007

Long interspersed element-1 protein expression is a hallmark of many human cancers

Am J Pathol. 2014 May;184(5):1280-6. doi: 10.1016/j.ajpath.2014.01.007. Epub 2014 Mar 6.

Authors

Nemanja Rodić¹, Reema Sharma², Rajni Sharma³, John Zampella⁴, Lixin Dai⁵, Martin S Taylor⁶, Ralph H Hruban⁷, Christine A Iacobuzio-Donahue⁷, Anirban Maitra⁸, Michael S Torbenson⁸, Michael Goggins⁹, Ie-Ming Shih¹⁰, Amy S Duffield¹¹, Elizabeth A Montgomery³, Edward Gabrielson³, George J Netto¹², Tamara L Lotan¹¹, Angelo M De Marzo¹², William Westra¹³, Zev A Binder¹⁴, Brent A Orr¹⁵, Gary L Gallia¹⁶, Charles G Eberhart¹⁷, Jef D Boeke¹⁸, Chris R Harris¹⁹, Kathleen H Burns²⁰

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: nrodic1@jhmi.edu.
² Department of Biochemistry and Molecular Biology, University of Maryland Baltimore County, Baltimore, Maryland.
³ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁴ Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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.
¹¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹² 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.
¹³ 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.
¹⁴ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁵ Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
¹⁶ 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.
¹⁷ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁸ 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.
¹⁹ 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.
²⁰ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Deoxyribonuclease I / metabolism*
Humans
Neoplasms / metabolism*
Neoplasms / pathology
Tumor Suppressor Protein p53 / deficiency
Tumor Suppressor Protein p53 / metabolism

Substances

Tumor Suppressor Protein p53
Deoxyribonuclease I
LINE-1 endonuclease, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding