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10th Anniversary of Biomedicines—DNA Sequences of Different Origins: Their Diagnostic...
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10th Anniversary of Biomedicines—DNA Sequences of Different Origins: Their Diagnostic and Therapeutical Applications

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 8137

Special Issue Editor

Dr. Ferenc Sipos

E-Mail Website
Guest Editor
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Interests: innate immunity; TLR9-signaling; autophagy; inflammation and cancer; inflammatory bowel disease; colorectal cancer; mucosal regeneration; immunology; gastroenterology; internal medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we aim to publish a Special Issue entitled 10th Anniversary of Biomedicines—DNA Sequences of Different Origins: Their Diagnostic and Therapeutical Applications.

Clinically visible tumors exhibit many genetic and epigenetic abnormalities, including DNA sequence modifications, chromosome copy number changes, and aberrant promoter hypermethylation, according to molecular studies of many forms of cancer. These abnormalities can be identified in premalignant lesions, as well as histologically normal neighboring cells in many circumstances. One of the major difficulties today is early detection, chemoprevention, and the development of new therapeutic techniques based on a better knowledge of cancer molecular alterations. DNA-based immunomodulatory sequences (DIMS) are prospective drugs for the treatment of a variety of disorders, including cancer and inflammation. They work by interacting with TLR9, a protein whose importance in innate immunity was recognized by the Nobel Prize in 2011. It has been demonstrated that the synthesis of certain tertiary structures by DIMS is linked to specific physiologic consequences such as immune cell activation, interferon induction, and disease progression delay. Furthermore, the capacity of selected DIMS compounds to generate certain tertiary structures, such as unmethylated deoxyribonucleotide CpG, must be considered as significant for biological activities as the existence of functional primary structure motifs. TLR9 can recognize non-CpG patterns and promote cellular activation when DNA is efficiently transported to TLR9, for example, by cationic lipids, according to recent research. Furthermore, new evidence suggests that TLR9-independent immunoactivation is possible. These discoveries are relevant to the development of DNA-based immunomodulators.

This Special Issue’s goal is to showcase the most up-to-date diagnostic and therapeutic applications of DNA sequences of varied sources and qualities in inflammation and cancer.

Dr. Ferenc Sipos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • DNA sequences
  • immune modulation
  • Toll-like receptors
  • cancer diagnostics
  • cancer therapy
  • inflammation
  • methylation

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Published Papers (3 papers)

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Research

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8 pages, 1895 KiB  
Article
Detection of BRCA1, and BRCA2 Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting
by Taylor Ryan McFarland, Vinay Mathew Thomas, Roberto Nussenzveig, Georges Gebrael, Nicolas Sayegh, Nishita Tripathi, Kamal Kant Sahu, Divyam Goel, Benjamin L. Maughan, Deepika Sirohi, Neeraj Agarwal and Umang Swami
Biomedicines 2022, 10(12), 3170; https://doi.org/10.3390/biomedicines10123170 - 7 Dec 2022
Cited by 1 | Viewed by 2617
Abstract
Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious BRCA1 and/or 2 mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for [...] Read more.
Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious BRCA1 and/or 2 mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of BRCA mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting. Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect. Results: The presence or absence of mutations in the BRCA gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0–232) months. BRCA mutation was present in the patient’s original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% [95% CI, 95.3–99.1%]. The adjusted concordance between metastatic samples and cfDNA was 93.5% [95% CI, 86.4–97.3%]. Of the patients who had a BRCA mutation detected in their prostate tissue, there was a 70% probability of detecting a BRCA mutation in the patient’s cfDNA as well. For patients who did not have a detectable BRCA mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%. Conclusion: There is a high level of concordance between tissue and blood for BRCA mutations. Testing cfDNA can provide reliable information on BRCA mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new BRCA mutation later in the disease course is a rare event. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—DNA Sequences of Different Origins: Their Diagnostic and Therapeutical Applications)
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7 pages, 246 KiB  
Article
Does a High-Risk (>1/50) Result for First-Trimester Combined Screening Always Entail Invasive Testing? Which Patients from This Group Might Benefit from cfDNA Testing?
by Rocío García-Jiménez, Irene Valero, Isabel Corrales-Gutiérrez, Reyes Granell, Carlota Borrero and José Antonio Sainz-Bueno
Biomedicines 2022, 10(10), 2579; https://doi.org/10.3390/biomedicines10102579 - 14 Oct 2022
Viewed by 1582
Abstract
Currently, cell-free DNA (cfDNA) is offered as part of a contingent screening for patients with a first-trimester combined test (FCT) risk between 1/50 and 1/250. However, most aneuploidies are within the group of patients with a risk above 1/10. An observational, retrospective, and [...] Read more.
Currently, cell-free DNA (cfDNA) is offered as part of a contingent screening for patients with a first-trimester combined test (FCT) risk between 1/50 and 1/250. However, most aneuploidies are within the group of patients with a risk above 1/10. An observational, retrospective, and multi-centric study was carried out, to evaluate the theorical performance of lowering the cut-off point for the high-risk group from 1/50 to 1/10. Out of the 25,920 patients included, 25,374 (97.9%) consented to the cfDNA contingent screening for aneuploidies. With the proposed strategy, knowing that the detection rate (DR) of cfDNA testing for trisomy 21 is 99.7%, the DR for trisomy 21 would have stayed in a 93.2%, just as it was with the current strategy. In this instance, 267 (1.1%) invasive tests would have been performed, while the current strategy had a total of 307 (1.2%). The false positive rate (FPR) rate would have stayed at 5.2% in both scenarios. In conclusion, the contingent screening of aneuploidies based in the result of the FCT, offering the analysis of cfDNA to patients with an intermediate risk after lowering the cut-off point from 1/50 to 1/10, is a valid alternative that might maintain the current detection rates and avoid the complications associated with invasive testing. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—DNA Sequences of Different Origins: Their Diagnostic and Therapeutical Applications)

Review

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24 pages, 2768 KiB  
Review
Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
by Györgyi Műzes, Bettina Bohusné Barta, Orsolya Szabó, Vanessza Horgas and Ferenc Sipos
Biomedicines 2022, 10(11), 2853; https://doi.org/10.3390/biomedicines10112853 - 8 Nov 2022
Cited by 8 | Viewed by 3212
Abstract
The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. [...] Read more.
The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders. Immunocompetent cells express pattern-recognition receptors on their cell membrane and cytoplasm. The majority of endogenous DNA is located intracellularly within nuclei and mitochondria. However, extracellular, cell-free DNA (cfDNA) can also be detected in a variety of diseases, such as autoimmune disorders and malignancies, which has sparked interest in using cfDNA as a possible biomarker. In recent years, the widespread use of liquid biopsies and the increasing demand for screening, as well as monitoring disease activity and therapy response, have enabled the revival of cfDNA research. The majority of studies have mainly focused on the function of cfDNA as a biomarker. However, research regarding the immunological consequences of cfDNA, such as its potential immunomodulatory or therapeutic benefits, is still in its infancy. This article discusses the involvement of various DNA-sensing receptors (e.g., absent in melanoma-2; Toll-like receptor 9; cyclic GMP–AMP synthase/activator of interferon genes) in identifying host cfDNA as a potent danger-associated molecular pattern. Furthermore, we aim to summarize the results of the experimental studies that we recently performed and highlight the immunomodulatory capacity of cfDNA, and thus, the potential for possible therapeutic consideration. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—DNA Sequences of Different Origins: Their Diagnostic and Therapeutical Applications)
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