MHC-I基因型限制了致癌突变的情况

Rachel Marty ¹, Saghar Kaabinejadian ², David Rossell ³

¹Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093, USA.
²Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
³Department of Economics & Business, Universitat Pompeu Fabra, 08002 Barcelona, Spain.
⁴Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
⁵Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA; Division of Molecular Oncology & Immunology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
⁶Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA.
⁷Cancer Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
⁸Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Cancer Cell Map Initiative (CCMI), University of California San Diego, La Jolla, CA 92093, USA; Department of Computer Science, University of California San Diego, La Jolla, CA 92093, USA.
⁹Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Cancer Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
¹⁰Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Cancer Cell Map Initiative (CCMI), University of California San Diego, La Jolla, CA 92093, USA.

⁰Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093, USA.

概括

人类白细胞抗原I类 (MHC-I) 呈现方式影响癌症突变. 患者的MHC- I基因型预测出哪些致癌突变,影响瘤发育和癌症易感性.

科学领域

免疫学
癌症学
遗传学

背景情况

人类白细胞抗原I类 (MHC-I) 分子向T细胞呈现细胞内,对免疫监测至关重要.
一个个体所拥有的特定的MHC-I基因组定义了其独特的子,影响了免疫识别.
一个人的MHC-I呈现中的"差距"可能会影响癌症的发展,使特定的突变能够逃避免疫检测.

研究的目的

调查人类白细胞抗原I类 (MHC-I) 呈现差异是否影响人类癌症的致癌突变的出现.
根据患者的MHC-I基因型和表现能力开发突变发生的预测模型.

主要方法

开发了一个以残留物为中心的患者表现得分.
分析了9176名癌症患者和1018例复发性瘤突变.
与瘤突变频率相关的患者MHC- I基因型呈现得分.

主要成果

基于患者MHC- I基因型的得分有效预测了瘤中出现特定突变的可能性.
在患者队列中发现MHC- I表现差的突变在瘤中更频繁.
证明了MHC-I基因型受限表现与观察到的致癌突变之间存在联系.

结论

人类白细胞抗原I类 (MHC-I) 基因型受限免疫编辑显著影响瘤形成过程中的致癌突变谱.
了解个体MHC-I表现能力可以帮助预测个体的癌症易感性.
这项研究开辟了基于MHC-I遗传学的个性化癌症风险评估的途径.

关键词:

抗原呈现方式癌症容易患上癌症癌症易感性预测人类白细胞抗原免疫编辑免疫学免疫疗法主要基因相容性综合体新抗原

MHC-I基因型限制了致癌突变的情况

概括

科学领域

背景情况

研究的目的

主要方法

主要成果

结论

关键词:

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MHC-I基因型限制了致癌突变的情况

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概括

科学领域

背景情况

研究的目的

主要方法

主要成果

结论

关键词:

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