Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i>
Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as <i>BRCA1</i> and <i>BRCA...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/45/8/418 |
| _version_ | 1797585126740197376 |
|---|---|
| author | Tara Zuhair Kassem Marius Wunderle Lukas Kuhlmann Matthias Ruebner Hanna Huebner Juliane Hoyer André Reis Peter A. Fasching Matthias W. Beckmann Carolin C. Hack Rainer Fietkau Luitpold Distel |
| author_facet | Tara Zuhair Kassem Marius Wunderle Lukas Kuhlmann Matthias Ruebner Hanna Huebner Juliane Hoyer André Reis Peter A. Fasching Matthias W. Beckmann Carolin C. Hack Rainer Fietkau Luitpold Distel |
| author_sort | Tara Zuhair Kassem |
| collection | DOAJ |
| description | Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as <i>BRCA1</i> and <i>BRCA2</i>. By studying the chromosomal radiosensitivity of <i>BRCA1/2</i> mutation carriers compared to the general population, we study whether increased chromosomal radiation sensitivity is observed in patients with <i>BRCA1/2</i> variants. Methods: Three-color-fluorescence in situ hybridization was performed on ex vivo-irradiated peripheral blood lymphocytes from 64 female patients with a heterozygous germline <i>BRCA1</i> or <i>BRCA2</i> mutation. Aberrations in chromosomes #1, #2 and #4 were analyzed. Mean breaks per metaphase (B/M) served as the parameter for chromosomal radiosensitivity. The results were compared with chromosomal radiosensitivity in a cohort of generally healthy individuals and patients with rectal cancer or breast cancer. Results: Patients with <i>BRCA1/2</i> mutations (<i>n</i> = 64; B/M 0.47) overall showed a significantly higher chromosomal radiosensitivity than general healthy individuals (<i>n</i> = 211; B/M 0.41) and patients with rectal cancer (<i>n</i> = 379; B/M 0.44) and breast cancer (<i>n</i> = 147; B/M 0.45) without proven germline mutations. Chromosomal radiosensitivity varied depending on the locus of the <i>BRCA1/2</i> mutation. Conclusions: <i>BRCA1/2</i> mutations result in slightly increased chromosomal sensitivity to radiation. A few individual patients have a marked increase in radiation sensitivity. Therefore, these patients are at a higher risk for adverse therapeutic consequences. |
| first_indexed | 2024-03-11T00:02:32Z |
| format | Article |
| id | doaj.art-9aebbc8e3c064932ba9791c9a8ea5e53 |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-11T00:02:32Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-9aebbc8e3c064932ba9791c9a8ea5e532023-11-19T00:41:56ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-08-014586618663310.3390/cimb45080418Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i>Tara Zuhair Kassem0Marius Wunderle1Lukas Kuhlmann2Matthias Ruebner3Hanna Huebner4Juliane Hoyer5André Reis6Peter A. Fasching7Matthias W. Beckmann8Carolin C. Hack9Rainer Fietkau10Luitpold Distel11Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyInstitute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 10, D-91054 Erlangen, GermanyInstitute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 10, D-91054 Erlangen, GermanyDepartment of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, GermanyBackground: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as <i>BRCA1</i> and <i>BRCA2</i>. By studying the chromosomal radiosensitivity of <i>BRCA1/2</i> mutation carriers compared to the general population, we study whether increased chromosomal radiation sensitivity is observed in patients with <i>BRCA1/2</i> variants. Methods: Three-color-fluorescence in situ hybridization was performed on ex vivo-irradiated peripheral blood lymphocytes from 64 female patients with a heterozygous germline <i>BRCA1</i> or <i>BRCA2</i> mutation. Aberrations in chromosomes #1, #2 and #4 were analyzed. Mean breaks per metaphase (B/M) served as the parameter for chromosomal radiosensitivity. The results were compared with chromosomal radiosensitivity in a cohort of generally healthy individuals and patients with rectal cancer or breast cancer. Results: Patients with <i>BRCA1/2</i> mutations (<i>n</i> = 64; B/M 0.47) overall showed a significantly higher chromosomal radiosensitivity than general healthy individuals (<i>n</i> = 211; B/M 0.41) and patients with rectal cancer (<i>n</i> = 379; B/M 0.44) and breast cancer (<i>n</i> = 147; B/M 0.45) without proven germline mutations. Chromosomal radiosensitivity varied depending on the locus of the <i>BRCA1/2</i> mutation. Conclusions: <i>BRCA1/2</i> mutations result in slightly increased chromosomal sensitivity to radiation. A few individual patients have a marked increase in radiation sensitivity. Therefore, these patients are at a higher risk for adverse therapeutic consequences.https://www.mdpi.com/1467-3045/45/8/418<i>BRCA1</i><i>BRCA2</i>breast cancerchromosomal radiosensitivityFISH assayradiation oncology |
| spellingShingle | Tara Zuhair Kassem Marius Wunderle Lukas Kuhlmann Matthias Ruebner Hanna Huebner Juliane Hoyer André Reis Peter A. Fasching Matthias W. Beckmann Carolin C. Hack Rainer Fietkau Luitpold Distel Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i> Current Issues in Molecular Biology <i>BRCA1</i> <i>BRCA2</i> breast cancer chromosomal radiosensitivity FISH assay radiation oncology |
| title | Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i> |
| title_full | Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i> |
| title_fullStr | Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i> |
| title_full_unstemmed | Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i> |
| title_short | Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes <i>BReast CAncer 1</i> and <i>BReast CAncer 2</i> |
| title_sort | ex vivo chromosomal radiosensitivity testing in patients with pathological germline variants in breast cancer high susceptibility genes i breast cancer 1 i and i breast cancer 2 i |
| topic | <i>BRCA1</i> <i>BRCA2</i> breast cancer chromosomal radiosensitivity FISH assay radiation oncology |
| url | https://www.mdpi.com/1467-3045/45/8/418 |
| work_keys_str_mv | AT tarazuhairkassem exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT mariuswunderle exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT lukaskuhlmann exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT matthiasruebner exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT hannahuebner exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT julianehoyer exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT andrereis exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT peterafasching exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT matthiaswbeckmann exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT carolinchack exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT rainerfietkau exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i AT luitpolddistel exvivochromosomalradiosensitivitytestinginpatientswithpathologicalgermlinevariantsinbreastcancerhighsusceptibilitygenesibreastcancer1iandibreastcancer2i |