Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells-Reference-Cited by-同舟云学术

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells

Published:2024-05-23 Issue:13 Volume:52 Page:7539-7555
ISSN:0305-1048
Container-title:Nucleic Acids Research
language:en
Short-container-title:

Author:

Cinar Munevver¹,Martinez-Medina Lourdes²,Puvvula Pavan K²,Arakelyan Arsen³,Vardarajan Badri N²,Anthony Neil⁴,Nagaraju Ganji P⁵,Park Dongkyoo¹,Feng Lei²,Sheff Faith⁶,Mosunjac Marina⁶,Saxe Debra⁶,Flygare Steven⁷,Alese Olatunji B¹,Kaufman Jonathan L¹,Lonial Sagar¹,Sarmiento Juan M⁸,Lossos Izidore S⁹^ORCID,Vertino Paula M¹⁰^ORCID,Lopez Jose A¹¹,El-Rayes Bassel⁵,Bernal-Mizrachi Leon¹^ORCID

Affiliation:

1. Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA, USA

2. Kodikaz Therapeutic Solutions, Inc , New York , NY, USA

3. Bioinformatics group, Institute of Molecular Biology NAS RA , Yerevan , Armenia

4. Integrated Cellular Imaging Core, Winship Cancer Institute of Emory University , Atlanta, GA, USA

5. Division of hematology and oncology, O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham , Birmingham, AL, USA

6. Pathology and Laboratory Medicine, Winship Cancer Institute of Emory University , Atlanta, GA, USA

7. Department of Computational Biology/ Genetics, The University of Utah , Salt Lake City, UT, USA

8. Department of Surgery, Winship Cancer Institute of Emory University , Atlanta, GA, USA

9. Department of Medicine, Division of Hematology-Oncology and Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami , Miami, FL, USA

10. Department of Biomedical Genetics and the Wilmot Cancer Institute, University of Rochester Medical Center , Rochester, NY, USA

11. Bloodworks Northwest Research Institute, Division of Hematology, University of Washington School of Medicine , Seattle, WA, USA

Abstract

Abstract The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.

Funder

Georgia Research Alliance Venture Development Award

National Cancer Institute

Dwoskin, and Anthony Rizzo Families Foundations

Jaime Erin Follicular Lymphoma Research Consortium

Clinical and Translational Science Award Program

National Institutes of Health

National Center for Advancing Translational Sciences

Winship Cancer Institute of Emory University

Publisher

Oxford University Press (OUP)

Link