Germline genetic biomarkers to stratify patients for personalized radiation treatment
Abstract Background Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or pati...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03561-x |
| _version_ | 1811215739858714624 |
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| author | Ida Deichaite Austin Hopper Lena Krockenberger Timothy J. Sears Leisa Sutton Xenia Ray Andrew Sharabi Ami Navon Parag Sanghvi Hannah Carter Vitali Moiseenko |
| author_facet | Ida Deichaite Austin Hopper Lena Krockenberger Timothy J. Sears Leisa Sutton Xenia Ray Andrew Sharabi Ami Navon Parag Sanghvi Hannah Carter Vitali Moiseenko |
| author_sort | Ida Deichaite |
| collection | DOAJ |
| description | Abstract Background Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes. Identifying potential biomarkers which can help predict toxicity, as well as response to treatment, is of significant interest. Methods Patients with HNSCC who received RT and underwent next generation sequencing of somatic tumor samples, transcriptome RNA-seq with matched normal tissue samples were included. Patients were then grouped by propensity towards increased late vs. early toxicity (Group A) and those without (Group B), assessed by CTCAE v5.0. The groups were then analyzed for association of specific germline variants with toxicity and clinical outcomes. Results In this study we analyzed 37 patients for correlation between germline variants and toxicity. We observed that TSC2, HLA-A, TET2, GEN1, NCOR2 and other germline variants were significantly associated with long term toxicities. 34 HNSCC patients treated with curative intent were evaluated for clinical outcomes. Group A had significantly improved overall survival as well as improved rates of locoregional recurrence and metastatic disease. Specific variants associated with improved clinical outcomes included TSC2, FANCD2, and PPP1R15A, while the HLA-A and GEN1 variants were not correlated with survival or recurrence. A group of five HLA-DMA/HLA-DMB variants was only found in Group B and was associated with a higher risk of locoregional recurrence. Conclusions This study indicates that germline genetic biomarkers may have utility in predicting toxicity and outcomes after radiation therapy and deserve further investigation in precision radiation medicine approaches. |
| first_indexed | 2024-04-12T06:27:24Z |
| format | Article |
| id | doaj.art-c721a2958deb4f2f84a533c644a085e3 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T06:27:24Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-c721a2958deb4f2f84a533c644a085e32022-12-22T03:44:06ZengBMCJournal of Translational Medicine1479-58762022-08-0120111310.1186/s12967-022-03561-xGermline genetic biomarkers to stratify patients for personalized radiation treatmentIda Deichaite0Austin Hopper1Lena Krockenberger2Timothy J. Sears3Leisa Sutton4Xenia Ray5Andrew Sharabi6Ami Navon7Parag Sanghvi8Hannah Carter9Vitali Moiseenko10Department of Radiation Medicine and Applied Sciences, University of California San DiegoDepartment of Radiation Medicine and Applied Sciences, University of California San DiegoMoores Cancer Center, University of California San DiegoBioinformatics and Systems Biology Program, University of California San DiegoMoores Cancer Center, University of California San DiegoDepartment of Radiation Medicine and Applied Sciences, University of California San DiegoDepartment of Radiation Medicine and Applied Sciences, University of California San DiegoDepartment of Biological Regulation, Weizmann Institute of ScienceDepartment of Radiation Medicine and Applied Sciences, University of California San DiegoMoores Cancer Center, University of California San DiegoDepartment of Radiation Medicine and Applied Sciences, University of California San DiegoAbstract Background Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes. Identifying potential biomarkers which can help predict toxicity, as well as response to treatment, is of significant interest. Methods Patients with HNSCC who received RT and underwent next generation sequencing of somatic tumor samples, transcriptome RNA-seq with matched normal tissue samples were included. Patients were then grouped by propensity towards increased late vs. early toxicity (Group A) and those without (Group B), assessed by CTCAE v5.0. The groups were then analyzed for association of specific germline variants with toxicity and clinical outcomes. Results In this study we analyzed 37 patients for correlation between germline variants and toxicity. We observed that TSC2, HLA-A, TET2, GEN1, NCOR2 and other germline variants were significantly associated with long term toxicities. 34 HNSCC patients treated with curative intent were evaluated for clinical outcomes. Group A had significantly improved overall survival as well as improved rates of locoregional recurrence and metastatic disease. Specific variants associated with improved clinical outcomes included TSC2, FANCD2, and PPP1R15A, while the HLA-A and GEN1 variants were not correlated with survival or recurrence. A group of five HLA-DMA/HLA-DMB variants was only found in Group B and was associated with a higher risk of locoregional recurrence. Conclusions This study indicates that germline genetic biomarkers may have utility in predicting toxicity and outcomes after radiation therapy and deserve further investigation in precision radiation medicine approaches.https://doi.org/10.1186/s12967-022-03561-xPredictive biomarkers of radiation toxicityHead and neck squamous cell carcinomaRadiogenomicsGermline variantsTSC2HLA-A |
| spellingShingle | Ida Deichaite Austin Hopper Lena Krockenberger Timothy J. Sears Leisa Sutton Xenia Ray Andrew Sharabi Ami Navon Parag Sanghvi Hannah Carter Vitali Moiseenko Germline genetic biomarkers to stratify patients for personalized radiation treatment Journal of Translational Medicine Predictive biomarkers of radiation toxicity Head and neck squamous cell carcinoma Radiogenomics Germline variants TSC2 HLA-A |
| title | Germline genetic biomarkers to stratify patients for personalized radiation treatment |
| title_full | Germline genetic biomarkers to stratify patients for personalized radiation treatment |
| title_fullStr | Germline genetic biomarkers to stratify patients for personalized radiation treatment |
| title_full_unstemmed | Germline genetic biomarkers to stratify patients for personalized radiation treatment |
| title_short | Germline genetic biomarkers to stratify patients for personalized radiation treatment |
| title_sort | germline genetic biomarkers to stratify patients for personalized radiation treatment |
| topic | Predictive biomarkers of radiation toxicity Head and neck squamous cell carcinoma Radiogenomics Germline variants TSC2 HLA-A |
| url | https://doi.org/10.1186/s12967-022-03561-x |
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