Germline genetic biomarkers to stratify patients for personalized radiation treatment.
Germline genetic biomarkers to stratify patients for personalized radiation treatment.
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DOI：
10.1186/s12967-022-03561-x
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发表时间：
2022-08-12
影响因子：
7.4
通讯作者：
Moiseenko, Vitali
中科院分区：
文献类型：
--
作者：
Deichaite, Ida;Hopper, Austin;Krockenberger, Lena;Sears, Timothy J.;Sutton, Leisa;Ray, Xenia;Sharabi, Andrew;Navon, Ami;Sanghvi, Parag;Carter, Hannah;Moiseenko, Vitali
关键词：
结合基因分析的精准医学正在成为医学肿瘤学的标准护理。然而，在放射肿瘤学领域，遗传分析的使用有限，并且种系遗传生物标志物对放射敏感性、放射抵抗性或放射治疗后患者结局的影响知之甚少。在HNSCC中，与治疗相关的毒性可能导致延迟或早期停止，这与更差的结果相关。识别可以帮助预测毒性以及对治疗的反应的潜在生物标志物具有重大意义。包括接受RT并接受体细胞肿瘤样品的下一代测序、转录组RNA-seq与匹配的正常组织样品的HNSCC患者。然后根据CTCAE v5.0评估的晚期与早期毒性增加倾向（A组）和无毒性增加倾向（B组）对患者进行分组。然后分析这些组的特定种系变异与毒性和临床结果的关联。在这项研究中，我们分析了37例患者的生殖系变异和毒性之间的相关性。我们观察到TSC 2、HLA-A、TET 2、GEN 1、NCOR 2和其他生殖系变异体与长期毒性显著相关。对34例接受根治性治疗的HNSCC患者的临床结局进行了评价。A组显著提高了总生存率，并提高了局部复发和转移性疾病的发生率。与改善临床结果相关的特定变体包括TSC 2，FANCD 2和PPP 1 R15 A，而HLA-A和GEN 1变体与生存或复发无关。仅在B组中发现了一组5种HLA-DMA/HLA-DMB变异体，并且与较高的局部复发风险相关。这项研究表明，生殖系遗传生物标志物可能在预测放射治疗后的毒性和结果方面具有实用性，值得在精确放射医学方法中进一步研究。
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. 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. 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. 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.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
64.5
作者：
Fekairi S;Scaglione S;Chahwan C;Taylor ER;Tissier A;Coulon S;Dong MQ;Ruse C;Yates JR 3rd;Russell P;Fuchs RP;McGowan CH;Gaillard PHL
通讯作者：
Gaillard PHL
影响因子：
28.2
作者：
Iglesias-Bartolome R;Martin D;Gutkind JS
通讯作者：
Gutkind JS
DOI：
10.1016/j.radonc.2016.06.017
发表时间：
2016-12
期刊：
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
影响因子：
--
作者：
Andreassen CN;Rosenstein BS;Kerns SL;Ostrer H;De Ruysscher D;Cesaretti JA;Barnett GC;Dunning AM;Dorling L;West CML;Burnet NG;Elliott R;Coles C;Hall E;Fachal L;Vega A;Gómez-Caamaño A;Talbot CJ;Symonds RP;De Ruyck K;Thierens H;Ost P;Chang-Claude J;Seibold P;Popanda O;Overgaard M;Dearnaley D;Sydes MR;Azria D;Koch CA;Parliament M;Blackshaw M;Sia M;Fuentes-Raspall MJ;Ramon Y Cajal T;Barnadas A;Vesprini D;Gutiérrez-Enríquez S;Mollà M;Díez O;Yarnold JR;Overgaard J;Bentzen SM;Alsner J;International Radiogenomics Consortium (RgC)
通讯作者：
International Radiogenomics Consortium (RgC)
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G