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肿瘤诊断焕发“芯”生！微阵列芯片快速分离、多重检测外泌体肿瘤标志物: nanomicrolett 2019-8-27 15:53; Rapid Isolation and Multiplexed Detection of Exosome Tumor Markers Via Queued Beads Combined with Quantum Dots in aMicroarray Yanan Bai, Yunxing Lu, Kun Wang, Zule Cheng, Youlan Qu, Shihui Qiu, Lin Zhou, Zhenhua Wu, Huiying Liu * , Jianlong Zhao * , Hongju Mao * Nano-Micro Lett. (2019) 11:59 https://doi.org/10.1007/s40820-019-0285-x 本文亮点 1 研究了一种基于微阵列的外泌体分离和多重肿瘤标志物检测方法； 2 捕获外泌体的微珠被均匀排布在微柱之间，避免了光学干扰，使测试结果更加准确； 3 不同类型的肺癌外泌体样品显示出独特的标志物表达水平。内容简介中国科学院上海微系统与信息技术研究所毛红菊老师开发了一种基于微珠捕获的微阵列芯片，用于外泌体分离和多重肿瘤标志物检测。（白亚楠博士为本文第一作者）该方法通过与微珠表面抗体结合来分离外泌体，然后这些微珠被均匀地排列在芯片中的微柱之间，并通过量子点（QD）探针检测外泌体上的肿瘤标志物。这种设计通过将光学信号分散到每颗微珠上，从而避免了光学干扰，使测试结果更为准确。同时分析了三种肺癌细胞和正常细胞培养上清液中的外泌体，并且采用三种QD探针标记不同肺癌标志物，对外泌体表面蛋白标志物进行多重检测。来源于肺癌细胞的荧光强度显著高于正常细胞（6~10倍），并且不同类型的肺癌细胞也显示出其独特的标记物表达水平。此外，使用该芯片对癌症患者的临床血样进一步验证，显示与常规血清标志物检测较好的一致性。这些结果为外泌体肿瘤标志物检测和早期肿瘤诊断提供了一种有前景的解决方案。研究背景肿瘤来源的外泌体积极参与肿瘤的发展和转移，并已成为液体活检中肿瘤诊断的一个潜在标志物。由于它们尺寸较小、机制复杂，且受限于当前分离和检测方法，因此影响了其研究的进展。与传统方法相比，微流体技术提供了更好的分析方法。图文导读 ▍ 细胞上清液外泌体肿瘤标志物多重检测单一的标志物检测使其在敏感性和特异性方面都受到了限制；因此，我们针对三种肺癌相关标志物进行了多重检测： CEA ，腺癌中最常见的广谱肿瘤蛋白标志物； Cyfra21-1 ，鳞状细胞癌常用标志物； ProGRP ，特异的，分泌活跃的小细胞肺癌细胞产物。使用抗CD9标记的微珠分离来自A549，H226，H446和HUVEC等细胞培养上清液的外泌体，并且分别用相应的肿瘤标志物抗体标记的三个QD探针用于检测微珠表面上的外泌体。从图1a中可以看出，肺癌细胞与正常细胞间的荧光强度存在较大差异（RPMI 1640作为阴性对照）。如图1b所示，我们对三种肺癌标志物的平均表达水平进行了分析。结果显示，与正常细胞相比，肺癌细胞显示出更高的荧光强度（6~10倍）。此外，不同的肺癌细胞显示出明显不同的标志物表达水平，根据各个肺癌蛋白标志物的表达情况可以初步实现对肺腺癌，肺鳞癌，小细胞肺癌这三种肺癌的分型, 这为进一步的肿瘤分类提供了可能。图1 (a) 不同细胞系外泌体使用三种不同的肿瘤特异性QD探针检测的荧光图像；(b) 三种肺癌标志物在不同细胞系的表达水平。 ▍ 血浆外泌体肿瘤标志物的检测验证进一步利用该芯片对临床血浆样本进行验证，检测样本包含10个临床肿瘤标志物检测异常的肺癌患者样本和10个健康对照样本。如图2a所示，肺癌样本标志物的表达水平显著高于健康对照组；然而，我们没有观察到不同肺癌类型与不同标志物表达水平的相关性，这可能是由于血浆样本的成分较为复杂以及检测样本较少。如图2b所示，我们采用了ROC曲线对诊断准确性进行了评估，结果显示CEA、Cyfra21-1和ProGRP的AUC分别为0.84、0.85和0.84。表明血浆外泌体在肺癌患者和健康对照的鉴别中具有较好的准确性。为了评估芯片的检测效果，我们将10例肺癌患者的CEA-QD探针表达水平与临床应用电化学发光免疫法检测的血液中CEA浓度进行了比较。结果如图2c所示，实验结果与临床数据有较好的一致性，说明我们检测方法的可靠性。图2 (a) 肺癌患者（方形）和健康对照（圆形）临床血浆外泌体的三种肿瘤标志物的表达水平；(b) 三种肺癌外泌体标记物多重检测的ROC曲线（CEA：AUC = 0.84，p =0.01；Cyfra21-1：AUC = 0.85，p = 0.008；ProGRP：AUC= 0.84，p = 0.01；置信区间为95%）；(c) 本方法测定的外泌体CEA表达水平与临床免疫法检测CEA浓度的比较。 / 总结 / 在本研究中，我们发展了一种新的微流控免疫分析系统用于外泌体的分离和肿瘤标志物检测，该系统采用微阵列芯片对微球进行均匀的排布。与现有的微流控方法相比，我们的芯片具有以下优点： (1) 本设计能够在相邻微柱间拦截微珠而不堵塞，避免游离荧光信号的干扰； (2) 采用QDs进行免疫检测，提高了荧光稳定性，并可进行多重生物标志物的检测； (3) 该芯片结构简单，分离检测简便，无需外场，可实现低成本快速检测。作者简介毛红菊（本文通讯作者）研究员、博士生导师中国科学院上海微系统与信息技术研究所传感技术联合国家重点实验室课题组负责人 ▍ 主要研究领域多年来一直从事生物传感器及纳米技术用于生物大分子检测的研究工作。 ▍ 主要研究成果负责研发的“丙型肝炎诊断试剂盒”获得了国家一类新药证书(国药证S20060022)，在临床上得到较好的应用。作为课题负责人及科研骨干，承担及参与了国家973计划、国家重点研发计划、中科院重大创新工程项目、国家自然科学基金和上海市重大项目等30多个重要项目，形成多项重要研究成果。现为国家重点研发计划、国家自然科学基金等项目课题负责人，负责多项国家重大课题的研究。近年来在本领域主流期刊及国内外会议发表论文100余篇，作为主要发明人申请及授权专利40余项，参编专著和教材5部（英文专著1部）。 E-mail: hjmao@mail.sim.ac.cn 白亚楠（本文第一作者）博士中国科学院上海微系统与信息技术研究所传感技术联合国家重点实验室 ▍ 主要研究领域主要从事微纳生物传感技术用于生物大分子检测的研究工作。 ▍ 主要研究成果作为科研骨干，参与了国家973计划、国家重点研发计划、中科院STS项目、上海市科委国际合作项目以及国家自然科学基金等多个重要项目的研发。在本领域主流期刊发表SCI论文10余篇，申请或授权发明专利5项。 E-mail: albert.bai@foxmail.com 相关阅读生物医学应用·往期回顾 👇 1 体内肿瘤的靶向检测与治疗：基于SiO2中空核-壳纳米结构的双模态PET/光学成像系统 2 肿瘤的光热及光动力联合治疗：吲哚菁绿色修饰的磁性普鲁士蓝纳米复合药物系统 3 癌症标志物检测：基于纳米牛血清白蛋白功能化的石墨烯生物传感器关于我们 Nano-Micro Letters是上海交通大学主办的英文学术期刊，主要报道纳米/微米尺度相关的最新高水平科研成果与评论文章及快讯，在Springer开放获取（open-access）出版。可免费获取全文，欢迎关注和投稿。 E-mail： editorial_office@nmletters.org Tel： 86-21-34207624; 4992 次阅读|0 个评论

微阵列数据分析的基因知识发现: xupeiyang 2010-12-27 10:39; Start A-Literature C-Literature B-list Filter Literature A-query: microarray C-query: hypothesis testing The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 128 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 24234 and can be accessed from the start page after you leave this session. There are 1640 terms on the current B-list ( 684 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. job id # 24234 started Sun Dec 26 21:24:53 2010 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 24234 Search ARROWSMITH A A_query_raw: microarray Sun Dec 26 21:26:15 2010 A query = microarray started Sun Dec 26 21:26:15 2010 A query resulted in 39857 titles 24234 Search ARROWSMITH C C_query_raw: hypothesis testing Sun Dec 26 21:26:26 2010 C: hypothesis testing 11558 A: pubmed_query_A 39857 AC: ( microarray ) AND ( hypothesis testing ) 128 C query = hypothesis testing started Sun Dec 26 21:26:26 2010 C query resulted in 11558 titles A AND C query resulted in 128 titles 20868 B-terms ready on Sun Dec 26 21:30:39 2010 Sem_filter: Genes Molecular Sequences, and Gene Protein Names 1640 B-terms left after filter executed Sun Dec 26 22:22:08 2010 1640 B-terms left after filter executed Sun Dec 26 22:22:09 2010 1640 B-terms left after filter executed Sun Dec 26 22:22:13 2010 B-list on Sun Dec 26 22:24:06 2010 1 brca2 2 brca1 3 genome scan 4 quantitative trait loci 5 single nucleotide polymorphism 6 drb1 7 microsatellite 8 gene ontology 9 quantitative trait locus 10 abca4 11 transporter gene 12 hepcidin 13 her-2 neu 14 cdkn2a 15 cox-2 16 promoter polymorphism 17 hla drb1 18 rankl 19 her2 20 jnk 21 mtor 22 caspase 23 pten 24 her-2 25 cyp2d6 26 akt 27 stat1 28 homeobox gene 29 mlh1 30 gene schizophrenia 31 adiponectin 32 homeobox 33 kai1 34 hla g 35 angiopoietin 36 nf2 37 stat3 38 wfs1 39 frataxin 40 map kinase 41 gdnf 42 cdna 43 fmr1 44 wnt 45 matrix metalloproteinase 46 serial analysis gene 47 aryl hydrocarbon receptor 48 differentially expressed gene 49 ret 50 leptin 51 runx2 52 operon 53 wt1 54 erbb2 55 myostatin 56 ppar 57 c myc 58 circadian gene 59 sod1 60 braf 61 metabolic syndrome 62 genome duplication 63 immediate early gene 64 gene family 65 early gene 66 genome wide 67 mt1-mmp 68 nkt 69 p38 70 ink4a 71 huntingtin 72 nf1 73 msh2 74 chemokine 75 16s 76 nf kappab 77 bdnf 78 snp 79 cftr 80 fhit 81 estrogen receptor alpha 82 tumor suppressor gene 83 abcr 84 mek 85 amphiregulin 86 virulence gene 87 cd34 88 gene cluster 89 receptor tyrosine kinase 90 carboxypeptidase e 91 p16 ink4a 92 card15 93 candidate gene 94 multigene 95 ltp 96 e6 97 ubiquitin conjugating enzyme 98 gstm1 99 hepatocyte growth factor 100 nod2 101 cadherin 102 cd117 103 rnai 104 tata binding protein 105 ghrelin 106 cancer susceptibility gene 107 ppar alpha 108 brca1 gene 109 socs3 110 ubiquitin 111 ppar gamma 112 p27 113 myocilin 114 p53 gene 115 gp120 116 connexin 117 transcription factor 118 microrna 119 xrcc1 120 sp1 121 ets 122 hnf-1alpha 123 polymorphism gene 124 fgfr3 125 aml1 126 gene environment 127 activin 128 autotaxin 129 gene associated schizophrenia 130 gene encoding 131 kappab gene 132 estrogen receptor beta 133 egfr 134 e selectin 135 il-8 136 e virus 137 cd8 138 fibrosis transmembrane conductance 139 contextual fear conditioning 140 e cadherin 141 susceptibility gene 142 progesterone receptor 143 igfbp-3 144 hox 145 gene breast cancer 146 tgf beta 147 enhancer 148 psa 149 nicotinamide n methyltransferase 150 chaperone 151 response element 152 erbb3 153 dqb1 154 exon 155 nod scid mice 156 polymorphism promoter 157 egfr tyrosine kinase 158 hla a 159 p16 160 traf2 161 nrf2 162 polycystic ovary syndrome 163 hdac6 164 nf1 gene 165 rrna 166 hfe 167 dmd 168 statin 169 caspase-3 170 reelin 171 signaling gene 172 cell cycle progression 173 serca2a 174 mrsa 175 slc26a4 176 estrogen receptor 177 e4 allele 178 dc sign 179 e7 180 foxp2 181 growth factor gene 182 gene association 183 exonic splicing enhancer 184 bcl xl 185 bax 186 endostatin 187 erbb-2 188 gucy2d 189 cx3cl1 190 schizophrenia susceptibility gene 191 dna repair gene 192 tenascin c 193 proneural gene 194 bp180 195 p300 196 titin 197 apc gene 198 cd11b 199 tyrosine kinase 200 calcium sensing receptor 201 mdr1 202 tumor suppressor 203 hdm2 204 vpr 205 urocortin 206 anova 207 myc gene 208 tnf alpha 209 resistance gene 210 gene transcript 211 polyposis coli gene 212 cd4 213 nf2 gene 214 human genome 215 imprinted gene 216 il-1beta 217 coli gene 218 intron 219 myc 220 rdna 221 tnfalpha 222 macrophage activation 223 cannabinoid receptor 224 abeta 225 caga 226 comt 227 histone deacetylase 228 peroxisome 229 nod 230 cytokine production 231 novel gene 232 rna binding protein 233 ccnd1 234 genomic library 235 p53 236 rpe65 237 aggrecan 238 cdkn1c 239 bmd 240 gene ovarian cancer 241 gad65 242 tag-72 243 factor gene 244 chemokine receptor 245 il-10 246 androgen receptor 247 bcl2 248 pkb akt 249 gelsolin 250 notch 251 caveolin-3 252 ifn 253 analysis gene 254 il-18 255 fhit gene 256 neu 257 sib 258 mitochondrial genome 259 hmga2 260 receptor gene expression 261 oncogene 262 gene colorectal cancer 263 tcdd 264 prion protein 265 th2 266 receptor gene 267 hdl 268 hupo 269 oct4 270 prb 271 methylation gene 272 rna binding 273 based snp 274 th1 275 mmp-1 276 gene autism 277 b27 278 ube3a 279 topoisomerase 280 math1 281 retinal degeneration 282 ror2 283 dna methylation gene 284 pseudogene 285 cell adhesion molecule 286 pink1 287 gene silencing 288 antioxidant response element 289 rho kinase 290 fuzzy 291 troponin 292 cytochrome p450 293 ivf 294 retinoic acid receptor 295 sos 296 angiotensin receptor 297 t7 298 oncogene tumor suppressor 299 mmp 300 protein sequence 301 ca1 302 hla 303 phospholamban 304 methylenetetrahydrofolate reductase 305 rt 306 gene associated 307 suppressor gene 308 str 309 glucocorticoid receptor 310 diabetic nephropathy 311 gene multiple sclerosis 312 ca125 313 pcr 314 ifn gamma 315 vitamin d receptor 316 igf 317 spatial learning 318 gene gastric 319 autophagy 320 apolipoprotein e 321 gene colorectal 322 erk 323 neu amplification 324 inflammatory gene 325 mitochondrial gene 326 c kit 327 tnf 328 based microsatellite 329 cyp1a1 330 cd59 331 retrotransposon 332 gene involved 333 epidermal growth factor 334 hox gene 335 uchl1 336 cd44 337 related gene 338 p450 339 cytokine 340 gene related 341 adenosine a2a receptor 342 leber congenital amaurosis 343 bcr abl 344 connexin43 345 integrin 346 cell cycle gene 347 analysis gene array 348 disease gene 349 caspase-2 350 selenoprotein 351 parkin 352 bcr 353 gene ovarian 354 cdk5 355 udp glucuronosyltransferase 356 bone morphogenetic protein 357 dynamin 358 trkb 359 extracellular matrix protein 360 plasticity related gene 361 gene bipolar 362 galectin 363 atopy 364 telangiectasia mutated gene 365 protein tyrosine phosphatase 366 haloperidol induced catalepsy 367 repetitive dna sequence 368 ctl 369 pcc 370 bacterial genome 371 genome based expression 372 insulin growth factor 373 nf 374 operon transcriptional 375 intron length 376 premature ovarian failure 377 gene japanese 378 uncoupling protein 379 rag1 380 heat shock protein 381 fdg 382 vaca 383 based allele 384 gene alzheimer 385 4p 386 c fos 387 motor neuron disease 388 foxg1 389 allelic variation 390 il-6 391 arabidopsis thaliana gene 392 methyltransferase 393 p53 tumor suppressor 394 mcp-1 395 fasl 396 allele 397 gene promoter 398 tyrosine phosphatase 399 xrcc3 400 wilm tumor 401 mannose binding lectin 402 interferon gamma 403 endothelin 404 tof 405 genomic imprinting 406 d3 receptor 407 helix turn helix 408 enzyme gene 409 trinucleotide repeat 410 pai-1 411 promoter 412 trail 413 n methyltransferase 414 diazepam binding inhibitor 415 aromatase 416 bcl 417 angiotensinogen gene 418 corticotropin releasing hormone 419 hla e 420 clock 421 epigenetic gene 422 glioma 423 lmna 424 mc1r 425 human gene 426 gene variant 427 sdhd 428 allelic 429 promoter region 430 xpa 431 meningioma 432 ssri 433 drd2 434 sars 435 reporter gene 436 il-12 437 p selectin 438 inferring gene 439 snca 440 myc oncogene 441 cox 442 gene primary hyperparathyroidism 443 apoe 444 isoform 445 igf i 446 factor kappab gene 447 ataxia telangiectasia mutated 448 abl 449 galanin 450 protein kinase 451 rapd 452 trka 453 ccr5 454 nr2b 455 transporter 456 s100 457 cd40 458 frameshift 459 adaptor 460 hsp90 461 globin gene 462 heme oxygenase 463 n cadherin 464 cleft lip 465 myopia 466 retinitis pigmentosa 467 igfbp-4 468 codon 469 impaired glucose tolerance 470 ampa 471 bone mineral density 472 gene chromosome 473 hemochromatosis 474 l myc 475 kit 476 c cbl 477 dopamine receptor 478 inflammatory bowel disease 479 gabaa 480 histocompatibility complex class 481 smurf1 482 linked gene 483 syndrome gene 484 subunit gene 485 seq 486 cd28 487 huntington disease 488 genetic code 489 gene p53 490 ugt2b17 491 gene associated bone 492 hyperparathyroidism 493 melanocortin receptor 494 filaggrin 495 wnt7a 496 tachykinin 497 ho-1 498 copd 499 gene cystic fibrosis 500 ctla4 501 her2 oncogene 502 s100b 503 genomic 504 cll 505 patched 506 anxiety related behavior 507 gene array 508 d1 509 tandem repeat 510 obese 511 il6 512 copy 513 neurotrophic factor gene 514 proinsulin 515 lps 516 lamin a c 517 cue 518 insulin receptor 519 nodal 520 shear 521 erbb 522 prostate cancer 523 analysis genome 524 arabinogalactan protein 525 glycogen synthase 526 bomb 527 glutamate receptor 528 reelin gene 529 pup 530 dioxygenase gene 531 fibroblast growth factor 532 adrb2 533 receptor kinase 534 gonadotropin releasing hormone 535 angiotensinogen 536 ornithine transcarbamylase 537 gaba a 538 il-17 539 gene response 540 vitronectin 541 ras 542 alzheimer disease 543 p glycoprotein 544 olfactory 545 promoter variant 546 early promoter 547 transposable element 548 senescence 549 association genome wide 550 gene pard3 551 xenobiotic metabolizing gene 552 lh 553 sumo1 554 mef2a 555 spinocerebellar ataxia 556 gene involved methionine 557 histone 558 paraoxonase 559 neurofibromatosis gene 560 gene transgenic 561 relation brca1 562 factor promoter 563 topoisomerase i 564 igf1r 565 conserved genomic 566 oncogene human 567 opioid receptor 568 thioredoxin 569 protein gene 570 tag 571 msh2 gene 572 hmgb1 573 anca 574 detection tumor suppressor 575 duplicate gene increase 576 lactase 577 myosin heavy chain 578 nr2a 579 transgene 580 igf-1 581 rna polymerase 582 btg1 583 metallothionein 584 hyperinsulinemia 585 rante 586 neurotrophin 587 biased gene 588 decorin 589 parvalbumin 590 il-12p40 591 gene a 592 e gene 593 d3 594 sf2 595 gaba a receptor 596 exonuclease 597 alfa 598 ip-10 599 interleukin 600 genome 601 egf 602 fgf2 603 nima 604 tgf alpha 605 bee 606 protein kinase c 607 retinoblastoma 608 deafness gene 609 icos 610 cd31 611 amyloid a 612 dna sequence 613 alpha7 614 glyoxalase i 615 c lectin 616 jc 617 lectin 618 vasp 619 glass 620 gene haplotype 621 adhd 622 pkb 623 craniosynostosis 624 grb10 625 catechol o-methyltransferase 626 lip 627 db 628 igfbp-5 629 somatostatin receptor 630 rna 631 radiation induced apoptosis 632 max 633 factor v 634 neuropeptide y 635 trna 636 replicase 637 nnos 638 cathepsin k 639 polymorphism human gene 640 altered gene 641 gpcr 642 trait 643 cd11b cd18 644 cuff 645 insulin gene 646 tau protein 647 pmma 648 inducible 649 growth hormone receptor 650 gene coding 651 er 652 variant gene 653 transmembrane protein 654 nude 655 oscillator 656 hla gene 657 rna sequence 658 thyrotropin releasing hormone 659 tau gene 660 p13 661 dst 662 interferon gamma receptor 663 determining gene 664 ldl 665 p21 666 huntington 667 calcium channel 668 cml 669 suppressor gene p53 670 gnrh 671 mrp2 672 locus 673 oxytocin receptor 674 iiia 675 rank 676 dynein 677 dr4 678 app 679 akt1 680 interleukin-10 gene 681 polycystic kidney disease 682 laterality 683 interferon 684 hsp27 http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/show_sentences.cgi Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature microarray brca2 hypothesis testing 1: Phytoestrogens regulate the expression of genes involved in different biological processes in BRCA2 knocked down MCF-7, MDA-MB-231 and MCF-10a cell lines.2010 Add to clipboard 2: Transcriptional characteristics of familial non-BRCA1 /BRCA2 breast tumors.2010 Add to clipboard 3: Arabidopsis BRCA2 and RAD51 proteins are specifically involved in defense gene transcription during plant immune responses.2010 Add to clipboard 4: Detection and precise mapping of germline rearrangements in BRCA1, BRCA2 , MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH).2008 Add to clipboard 5: Novel de novo BRCA2 mutation in a patient with a family history of breast cancer.2008 Add to clipboard 6: BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarray s.2007 Add to clipboard 7: Accurate prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage.2006 Add to clipboard 8: Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families.2005 Add to clipboard 9: Down-regulation of UCRP and UBE2L6 in BRCA2 knocked-down human breast cells.2005 Add to clipboard 10: Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers.2005 Add to clipboard 11: Relationship of patients' age to histopathological features of breast tumours in BRCA1 and BRCA2 and mutation-negative breast cancer families.2005 Add to clipboard 12: Molecular classification of familial non-BRCA1 /BRCA2 breast cancer.2003 Add to clipboard 13: Immunohistochemical characteristics defined by tissue microarray of hereditary breast cancer not attributable to BRCA1 or BRCA2 mutations: differences from breast carcinomas arising in BRCA1 and BRCA2 mutation carriers.2003 Add to clipboard 14: Universal DNA array detection of small insertions and deletions in BRCA1 and BRCA2 .2000 Add to clipboard 15: Mutation detection in K-ras, BRCA1, BRCA2 , and p53 using PCR/LDR and a universal DNA microarray .2000 Add to clipboard; 个人分类: 知识发现|4589 次阅读|0 个评论

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