Objective: Predicting malignant transformation (MT) in oral epithelial dysplasia (OED) is challenging. The higher rate of MT reported in nonsmokers suggests an endogenous etiology in oncogenesis. We hypothesize that loss of FANCD2 and associated proteins could influence genomic instability and MT in the absence of environmental carcinogens.
Study Design: Longitudinal archival samples were obtained from 40 individuals with OED: from diagnosis to the most recent review in 23 patients with stable OED or until excision of the squamous cell carcinoma in 17 patients with unstable OED undergoing MT. Histopathological reassessment, immunohistochemistry for FANCD2, and Western blotting for phosphorylation/monoubiquitylation status of ATR, CHK1, FANCD2, and FANCG were undertaken on each tissue sample.
Results: Decreased expression of FANCD2 was observed in the diagnostic biopsies of OED lesions that later underwent MT. Combining the FANCD2 expression scores with histologic grading more accurately predicted MT (P = .005) than histology alone, and it correctly predicted MT in 10 of 17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1, and pFANCG was observed in unstable OED.
Conclusions: There is preliminary evidence that defects in the DNA damage sensing/signaling/repair cascade are associated with MT in OED. Loss of expression of FANCD2 protein in association with a higher histologic grade of dysplasia offered better prediction of MT than clinicopathologic parameters alone.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.oooo.2021.07.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioactivated Glucoraphanin Improves Cell Survival, Upregulating Phospho-AKT, and Modulates Genes Involved in DNA Repair in an In Vitro Alzheimer's Disease Model: A Network-Transcriptomic Analysis.
Nutrients
December 2024
IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Background/objectives: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, for which a definitive cure is still missing. Recently, natural compounds have been investigated for their possible neuroprotective role, including the bioactivated product of glucoraphanin (GRA), the sulforaphane (SFN), which is highly rich in cruciferous vegetables. It is known that SFN alleviates neuronal dysfunction, apoptosis, and oxidative stress in the brain.
View Article and Find Full Text PDFHepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates.
Pathol Res Pract
November 2024
Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy. Electronic address:
Article Synopsis
- Hepatoid thymic carcinoma (HTC) is a rare tumor that looks similar to liver cancer, specifically found in the thymus gland, and a new case has been identified in a 40-year-old man with polycythemia vera.
- This case involved advanced analysis of the tumor's molecular profile, noting the presence of various proteins through immunohistochemistry and significant mutations identified via whole exome sequencing.
- The study suggests that HTC may represent an evolutionary shift in tumor characteristics, combining features of both thymic carcinoma and hepatoid tumors, indicated by the unique mutation patterns found in the cells.
FANCD2 genome binding is nonrandom and is enriched at large transcriptionally active neural genes prone to copy number variation.
Funct Integr Genomics
October 2024
Department of Cell and Molecular Biology, University of Rhode Island, 379 Center for Biotechnology and Life Sciences, 120 Flagg Road, Kingston, RI, USA.
Article Synopsis
- Fanconi anemia (FA) is a rare genetic disorder linked to congenital issues and an increased risk of cancer and bone marrow failure, with neurological problems becoming more prominent, known as Fanconi Anemia Neurological Syndrome (FANS).
- The study aims to clarify the role of the FANCD2 protein and the FA pathway using advanced genomics techniques.
- Findings reveal that FANCD2 selectively binds to important areas of the genome, particularly at gene start sites and large neural genes related to brain development, potentially explaining its role in maintaining the stability of these genes amid replication stress.
NuRD chromatin remodeling is required to repair exogenous DSBs in the germline.
bioRxiv
September 2024
Department of Biological Sciences, University of Massachusetts Lowell, 198 Riverside Dr. Lowell MA, 01854.
Organisms rely on coordinated networks of DNA repair pathways to protect genomes against toxic double-strand breaks (DSBs), particularly in germ cells. All repair mechanisms must successfully negotiate the local chromatin environment in order to access DNA. For example, nucleosomes can be repositioned by the highly conserved Nucleosome Remodeling and Deacetylase (NuRD) complex.
View Article and Find Full Text PDFFance deficiency impaired DNA damage repair of prospermatogonia and altered the repair dynamics of spermatocytes.
Reprod Biol Endocrinol
August 2024
Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, China.
Background: Non-obstructive azoospermia (NOA) is the most severe form of male infertility and affects approximately 1% of men worldwide. Fanconi anemia (FA) genes were known for their essential role in DNA repair and growing evidence showed the crucial role of FA pathway in NOA. However, the underlying mechanisms for Fance deficiency lead to a serious deficit and delayed maturation of male germ cells remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!