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Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Jun 03; Vol. 65 (6), pp. 7. - Publication Year :
- 2024
-
Abstract
- Purpose: The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status.<br />Methods: A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization.<br />Results: The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05).<br />Conclusions: Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.
- Subjects :
- Humans
Female
Male
Middle Aged
Aged
Adult
Aged, 80 and over
In Situ Hybridization, Fluorescence
In Situ Nick-End Labeling
Radiotherapy Dosage
Immunohistochemistry
Radiosurgery adverse effects
Radiosurgery methods
Dose-Response Relationship, Radiation
Uveal Neoplasms radiotherapy
Uveal Neoplasms genetics
Melanoma radiotherapy
Melanoma genetics
Chromosomes, Human, Pair 3 genetics
DNA Damage
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 65
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 38833258
- Full Text :
- https://doi.org/10.1167/iovs.65.6.7