Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers.
Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers.
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DOI：
10.1002/prca.201500096
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Anderson KS
中科院分区：
文献类型：
--
作者：
Katchman BA;Barderas R;Alam R;Chowell D;Field MS;Esserman LJ;Wallstrom G;LaBaer J;Cramer DW;Hollingsworth MA;Anderson KS
TP 53的突变在一部分癌症患者中诱导自身抗体免疫反应，这已被提议作为早期检测的生物标志物。在这里，我们研究了p53特异性自身抗体与多种肿瘤亚型的相关性，并确定了与p53突变状态和表位特异性的相关性。采用可编程ELISA法对412例浆液性卵巢癌、胰腺癌和乳腺癌患者的血清样本中的IgG p53自身抗体（p53-AAb）进行定量。为了确定患者是否产生突变特异性自身抗体，我们设计了一组最相关的51 p53点突变蛋白，以显示在定制的可编程蛋白质微阵列上。为了确定表位特异性，我们展示了跨越野生型p53蛋白长度的12个重叠平铺片段和38个N-和C-末端缺失。我们检测p53-AAb的敏感性为58.8%（卵巢癌），22%（胰腺癌），32%（三阴性乳腺癌）和10.2%（HER 2+乳腺癌），特异性为94%。p53-AAb的血清含有对51个展示的p53突变蛋白的广泛反应性自身抗体，表明对共同表位的多克隆应答。所有p53-AAb均对N-和C-末端的连续和不连续表位以及DNA结合结构域表现出广泛的多克隆免疫应答。在这项综合分析中，肿瘤p53突变诱导了具有广泛反应性表位特异性的强多克隆自身抗体。
Mutations in TP53 induce autoantibody immune responses in a subset of cancer patients, which have been proposed as biomarkers for early detection. Here, we investigate the association of p53-specific autoantibodies with multiple tumor subtypes and determine the association with p53 mutation status and epitope specificity. IgG p53 autoantibodies (p53-AAb), were quantified in 412 serum samples using a programmable ELISA assay from patients with serous ovarian, pancreatic adenocarcinoma, and breast cancer. To determine if patients generated mutation-specific autoantibodies we designed a panel of the most relevant 51 p53 point mutant proteins, to be displayed on custom programmable protein microarrays. To determine the epitope specificity we displayed 12 overlapping tiling fragments and 38 N- and C-terminal deletions spanning the length of the wild-type p53 protein. We detected p53-AAb with sensitivities of 58.8% (ovarian), 22% (pancreatic), 32% (triple negative breast cancer), and 10.2% (HER2+ breast cancer) at 94% specificity. Sera with p53-AAb contained broadly reactive autoantibodies to 51 displayed p53 mutant proteins, demonstrating a polyclonal response to common epitopes. All p53-AAb displayed broad polyclonal immune response to both continuous and discontinuous epitopes at the N- and C-terminus as well as the DNA-binding domain. In this comprehensive analysis, mutations in tumor p53 induce strong, polyclonal autoantibodies with broadly reactive epitope specificity.
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影响因子：
3.8
作者：
Esserman, Laura J.;Berry, Donald A.;Cheang, Maggie C. U.;Yau, Christina;Perou, Charles M.;Carey, Lisa;DeMichele, Angela;Gray, Joe W.;Conway-Dorsey, Kathleen;Lenburg, Marc E.;Buxton, Meredith B.;Davis, Sarah E.;van't Veer, Laura J.;Hudis, Clifford;Chin, Koei;Wolf, Denise;Krontiras, Helen;Montgomery, Leslie;Tripathy, Debu;Lehman, Constance;Liu, Minetta C.;Olopade, Olufunmilayo I.;Rugo, Hope S.;Carpenter, John T.;Livasy, Chad;Dressler, Lynn;Chhieng, David;Singh, Baljit;Mies, Carolyn;Rabban, Joseph;Chen, Yunni-Yi;Giri, Dilip;Au, Alfred;Hylton, Nola
通讯作者：
Hylton, Nola
DOI：
10.1158/1055-9965.epi-09-0880
发表时间：
2010-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Anderson KS;Wong J;Vitonis A;Crum CP;Sluss PM;Labaer J;Cramer D
通讯作者：
Cramer D
影响因子：
8.8
作者：
Pedersen, J. W.;Gentry-Maharaj, A.;Fourkala, E-O;Dawnay, A.;Burnell, M.;Zaikin, A.;Pedersen, A. E.;Jacobs, I.;Menon, U.;Wandall, H. H.
通讯作者：
Wandall, H. H.
DOI：
10.1007/s00262-009-0733-4
发表时间：
2009-10
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Reuschenbach M;von Knebel Doeberitz M;Wentzensen N
通讯作者：
Wentzensen N
影响因子：
4.4
作者：
Anderson, Karen S.;Ramachandran, Niroshan;LaBaer, Joshua
通讯作者：
LaBaer, Joshua