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Fusion gene

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307:. A major distinctive feature of the purine biosynthetic pathways in Bacteria is the prevalence of gene fusions where two or more purine biosynthetic enzymes are encoded by a single gene. Such gene fusions are almost exclusively between genes that encode enzymes that perform sequential steps in the biosynthetic pathway. Eukaryotic species generally exhibit the most common gene fusions seen in the Bacteria, but in addition have new fusions that potentially increase metabolic flux. 66: 332:
to the regulatory elements of genes of interest allows researches to study gene expression. Reporter gene fusions can be used to measure activity levels of gene regulators, identify the regulatory sites of genes (including the signals required), identify various genes that are regulated in response
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Gene fusion plays a key role in the evolution of gene architecture. We can observe its effect if gene fusion occurs in coding sequences. Duplication, sequence divergence, and recombination are the major contributors at work in gene evolution. These events can probably produce new genes from already
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sequence of another gene. If it happens in coding sequences, gene fusion cause the assembly of a new gene, then it allows the appearance of new functions by adding peptide modules into a multi-domain protein. The detecting methods to inventory gene fusion events on a large biological scale can
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It has been known for 30 years that the corresponding gene fusion plays an important role in tumorigenesis. Fusion genes can contribute to tumor formation because fusion genes can produce much more active abnormal protein than non-fusion genes. Often, fusion genes are
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Since chromosomal translocations play such a significant role in neoplasia, a specialized database of chromosomal aberrations and gene fusions in cancer has been created. This database is called Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.
167:, often occurring in prostate cancer. In the case of TMPRSS2-ERG, by disrupting androgen receptor (AR) signaling and inhibiting AR expression by oncogenic ETS transcription factor, the fusion product regulates the prostate cancer. Most fusion genes are found from 315:
In recent years, next generation sequencing technology has already become available to screen known and novel gene fusion events on a genome wide scale. However, the precondition for large scale detection is a paired-end sequencing of the cell's
320:. The direction of fusion gene detection is mainly towards data analysis and visualization. Some researchers already developed a new tool called Transcriptome Viewer (TViewer) to directly visualize detected gene fusions on the transcript level. 667:
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. (October 2005). "Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer".
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to the same stimulus, and artificially control the expression of desired genes in particular cells. For example, by creating a fusion gene of a protein of interest and
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Presence of certain chromosomal aberrations and their resulting fusion genes is commonly used within cancer diagnostics in order to set a precise diagnosis. Chromosome
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Oncogenic fusion genes may lead to a gene product with a new or different function from the two fusion partners. Alternatively, a proto-oncogene is fused to a strong
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existing parts. When gene fusion happens in non-coding sequence region, it can lead to the misregulation of the expression of a gene now under the control of the
246:(RT-PCR) are common methods employed at diagnostic laboratories. These methods all have their distinct shortcomings due to the very complex nature of cancer 1404:
Prendergast FG, Mann KG (August 1978). "Chemical and physical properties of aequorin and the green fluorescent protein isolated from Aequorea forskĂĄlea".
110:, and not through a simple deletion of chromosome 22 as was previously thought. Several investigators in the early 1980s showed that the Philadelphia 1470:: a new, comprehensive database of human CR events and associated diseases (both tumor and non-tumor) with detailed documentation of the CR events. 1508: 243: 1655: 180: 295:. Biosynthesis of these purines occurs by similar, but not identical, pathways in different species of the three domains of life, the 122:
in the breakpoint in chromosome 22. In 1985 it was clearly established that the fusion gene on chromosome 22 produced an abnormal
1461: 1191:"Genes linked by fusion events are generally of the same functional category: a systematic analysis of 30 microbial genomes" 398: 1476: 908: 78:
The first fusion gene was described in cancer cells in the early 1980s. The finding was based on the discovery in 1960 by
1501: 1483:: a database relates chromosomal aberrations to tumor characteristics, based either on individual cases or associations. 1388: 235: 428:
Mitelman F, Johansson B, Mertens F (April 2007). "The impact of translocations and gene fusions on cancer causation".
809: 720:"An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression" 1103:
Eichler EE (November 2001). "Recent duplication, domain accretion and the dynamic mutation of the human genome".
858:"Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples" 195: 1494: 1486: 102:
in Chicago showed that the Philadelphia chromosome had originated through a translocation between chromosomes
148: 1451: 17: 1467: 1140:"Functional associations of proteins in entire genomes by means of exhaustive detection of gene fusions" 1291:"Surveying purine biosynthesis across the domains of life unveils promising drug targets in pathogens" 821:
Vega F, Medeiros LJ (September 2003). "Chromosomal translocations involved in non-Hodgkin lymphomas".
58:. The identification of these fusion genes play a prominent role in being a diagnostic and prognostic 1596: 1552: 618: 520: 334: 43: 1591: 1521: 1380: 393: 168: 111: 91: 94:—the first consistent chromosome abnormality detected in a human malignancy, later designated the 1547: 1525: 403: 144: 95: 378: 268: 992:"A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis" 1576: 1542: 990:
Skotheim RI, Thomassen GO, Eken M, Lind GE, Micci F, Ribeiro FR, et al. (January 2009).
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Maher CA, Kumar-Sinha C, Cao X, Kalyana-Sundaram S, Han B, Jing X, et al. (March 2009).
184: 164: 107: 51: 1372: 1250:"Gene fusion/fission is a major contributor to evolution of multi-domain bacterial proteins" 1601: 1202: 1057: 946: 676: 633: 535: 103: 328:
Biologists may also deliberately create fusion genes for research purposes. The fusion of
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Supper J, Gugenmus C, Wollnik J, Drueke T, Scherf M, Hahn A, et al. (January 2013).
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caused by the strong promoter of the upstream fusion partner. The latter is common in
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led to the formation of a new BCR::ABL1 fusion gene, composed of the 3' part of the
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Nacu S, Yuan W, Kan Z, Bhatt D, Rivers CS, Stinson J, et al. (January 2011).
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Proceedings of the National Academy of Sciences of the United States of America
912: 383: 355: 338: 255: 251: 215: 211: 203: 123: 59: 735: 488: 1644: 571:"Fusion genes and chromosome translocations in the common epithelial cancers" 368: 329: 317: 688: 1624: 1571: 1357: 1316: 1275: 1234: 1215: 1175: 1124: 1089: 1027: 976: 893: 874: 842: 788: 753: 696: 653: 596: 555: 506: 449: 292: 231: 99: 79: 69:
A schematic showing the ways a fusion gene can occur at a chromosomal level
1008: 54:. Fusion genes have been found to be prevalent in all main types of human 42:
formed from two previously independent genes. It can occur as a result of
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Teixeira MR (December 2006). "Recurrent fusion oncogenes in carcinomas".
1425: 1417: 958: 909:"Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer" 126:
BCR::ABL1 protein with the capacity to induce chronic myeloid leukemia.
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gene in the breakpoint on chromosome 9 and the 5' part of a gene called
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Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, et al. (May 2010).
346: 160: 87: 587: 570: 1563: 304: 55: 1046:"Fusion and fission of genes define a metric between fungal genomes" 441: 65: 1517: 932: 300: 272:
provide insights about the multi modular architecture of proteins.
199: 136: 31: 1445:: The Improved Database of Chimeric Ttanscripts and RNA-seq Data. 296: 288: 284: 172: 156: 291:
are two of the four information encoding bases of the universal
1442: 666: 281: 247: 152: 140: 1458:: The Server Protein-Protein Interaction of Chimeric Proteins. 1448: 194:, and thereby the oncogenic function is set to function by an 1611: 1329: 935:"Transcriptome sequencing to detect gene fusions in cancer" 183:
is a fusion gene that is specific and unique to high-grade
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bear promise of introduction of more efficient methods.
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Gene formed by the combination of two independent genes
1043: 1247: 470: 1044:Durrens P, Nikolski M, Sherman D (October 2008). 473:"Oncogenic gene fusions in epithelial carcinomas" 1642: 1379:(4th ed.). New York: McGraw-Hill. pp.  1188: 855: 349:. The protein synthesized when a fusion gene is 1403: 1137: 823:Archives of Pathology & Laboratory Medicine 244:reverse transcription polymerase chain reaction 1039: 1037: 423: 421: 419: 1502: 1248:Pasek S, Risler JL, BrĂ©zellec P (June 2006). 477:Current Opinion in Genetics & Development 337:, the protein of interest may be observed in 820: 471:Prensner JR, Chinnaiyan AM (February 2009). 1464:: a knowledgebase for fusion genes updated. 1034: 717: 416: 86:in Philadelphia of a small abnormal marker 1509: 1495: 1288: 810:Deciphering the Cancer Transcriptome. 2016 1371:Hartwell, Leland H.; et al. (2011). 1347: 1306: 1265: 1224: 1214: 1165: 1155: 1079: 1069: 1017: 1007: 966: 883: 873: 743: 586: 496: 1370: 1332:"Detecting and visualizing gene fusions" 1189:Yanai I, Derti A, DeLisi C (July 2001). 766: 323: 64: 1102: 568: 14: 1643: 275: 1490: 1375:Genetics : from genes to genomes 1289:Chua SM, Fraser JA (November 2020). 907:Mitelman F; Johansson B; Mertens F. 399:List of RNA-Seq bioinformatics tools 1656:Modification of genetic information 24: 25: 1667: 1436: 632:(3438): 1488–501. November 1960. 534:(3438): 1488–501. November 1960. 163:with an interstitial deletion on 151:with t(12 ; 21)), AML1-ETO ( 1157:10.1186/gb-2001-2-9-research0034 1138:Enright AJ, Ouzounis CA (2001). 781:10.1615/critrevoncog.v12.i3-4.40 1397: 1364: 1323: 1282: 1241: 1182: 1131: 1096: 983: 926: 900: 849: 814: 769:Critical Reviews in Oncogenesis 803: 760: 711: 660: 619:"National Academy of Sciences" 611: 562: 521:"National Academy of Sciences" 513: 464: 250:. Recent developments such as 225: 13: 1: 1295:Immunology & Cell Biology 1267:10.1093/bioinformatics/btl135 1117:10.1016/s0168-9525(01)02492-1 646:10.1126/science.132.3438.1488 548:10.1126/science.132.3438.1488 409: 1071:10.1371/journal.pcbi.1000200 835:10.5858/2003-127-1148-CTIINL 310: 261: 129: 7: 1349:10.1016/j.ymeth.2012.09.013 569:Edwards PA (January 2010). 362: 10: 1672: 1050:PLOS Computational Biology 252:high-throughput sequencing 155:with t(8 ; 21)), and 73: 1610: 1597:Sister chromatid exchange 1561: 1532: 736:10.1016/j.ccr.2010.03.018 489:10.1016/j.gde.2008.11.008 335:green fluorescent protein 1592:Horizontal gene transfer 1522:homologous recombination 575:The Journal of Pathology 394:Horizontal gene transfer 112:chromosome translocation 92:chronic myeloid leukemia 1526:mobile genetic elements 689:10.1126/science.1117679 404:Mobile genetic elements 96:Philadelphia chromosome 1216:10.1073/pnas.141236298 875:10.1186/1755-8794-4-11 379:ETV6-NTRK3 gene fusion 210:may also be caused by 70: 1577:Chromosomal crossover 1009:10.1186/1476-4598-8-5 430:Nature Reviews Cancer 324:Research applications 185:serous ovarian cancer 169:hematological cancers 68: 52:chromosomal inversion 48:interstitial deletion 862:BMC Medical Genomics 1418:10.1021/bi00610a004 1207:2001PNAS...98.7940Y 1150:(9): RESEARCH0034. 1062:2008PLSCB...4E0200D 959:10.1038/nature07638 951:2009Natur.458...97M 681:2005Sci...310..644T 638:1960Sci...132.1488. 540:1960Sci...132.1488. 345:using fluorescence 276:Purine biosynthesis 1479:2016-05-25 at the 1454:2021-11-10 at the 1308:10.1111/imcb.12389 1105:Trends in Genetics 374:De novo gene birth 208:fusion transcripts 165:chromosome 21 71: 1638: 1637: 1474:Mitelman Database 588:10.1002/path.2632 206:genes. Oncogenic 90:in patients with 16:(Redirected from 1663: 1511: 1504: 1497: 1488: 1487: 1430: 1429: 1401: 1395: 1394: 1378: 1368: 1362: 1361: 1351: 1327: 1321: 1320: 1310: 1286: 1280: 1279: 1269: 1245: 1239: 1238: 1228: 1218: 1186: 1180: 1179: 1169: 1159: 1135: 1129: 1128: 1100: 1094: 1093: 1083: 1073: 1056:(10): e1000200. 1041: 1032: 1031: 1021: 1011: 996:Molecular Cancer 987: 981: 980: 970: 945:(7234): 97–101. 930: 924: 923: 921: 920: 911:. Archived from 904: 898: 897: 887: 877: 853: 847: 846: 818: 812: 807: 801: 800: 764: 758: 757: 747: 715: 709: 708: 664: 658: 657: 623: 615: 609: 608: 590: 566: 560: 559: 525: 517: 511: 510: 500: 468: 462: 461: 425: 389:Gene duplication 232:banding analysis 143:; these include 84:David Hungerford 21: 1671: 1670: 1666: 1665: 1664: 1662: 1661: 1660: 1641: 1640: 1639: 1634: 1620:Antigenic shift 1606: 1582:Gene conversion 1557: 1528: 1515: 1481:Wayback Machine 1456:Wayback Machine 1439: 1434: 1433: 1412:(17): 3448–53. 1402: 1398: 1391: 1369: 1365: 1328: 1324: 1301:(10): 819–831. 1287: 1283: 1260:(12): 1418–23. 1246: 1242: 1187: 1183: 1136: 1132: 1101: 1097: 1042: 1035: 988: 984: 931: 927: 918: 916: 905: 901: 854: 850: 819: 815: 808: 804: 775:(3–4): 257–71. 765: 761: 716: 712: 675:(5748): 644–8. 665: 661: 621: 617: 616: 612: 567: 563: 523: 519: 518: 514: 469: 465: 442:10.1038/nrc2091 426: 417: 412: 365: 326: 313: 278: 264: 256:DNA microarrays 228: 177:prostate cancer 132: 76: 28: 23: 22: 15: 12: 11: 5: 1669: 1659: 1658: 1653: 1636: 1635: 1633: 1632: 1627: 1622: 1616: 1614: 1608: 1607: 1605: 1604: 1599: 1594: 1589: 1584: 1579: 1574: 1568: 1566: 1559: 1558: 1556: 1555: 1553:Transformation 1550: 1545: 1539: 1537: 1530: 1529: 1514: 1513: 1506: 1499: 1491: 1485: 1484: 1471: 1465: 1459: 1446: 1438: 1437:External links 1435: 1432: 1431: 1396: 1390:978-0073525266 1389: 1363: 1322: 1281: 1254:Bioinformatics 1240: 1201:(14): 7940–5. 1181: 1144:Genome Biology 1130: 1095: 1033: 982: 925: 899: 848: 829:(9): 1148–60. 813: 802: 759: 710: 659: 610: 561: 512: 463: 414: 413: 411: 408: 407: 406: 401: 396: 391: 386: 384:Exon shuffling 381: 376: 371: 364: 361: 356:fusion protein 330:reporter genes 325: 322: 312: 309: 277: 274: 269:cis-regulatory 263: 260: 227: 224: 212:trans-splicing 204:immunoglobulin 131: 128: 75: 72: 26: 9: 6: 4: 3: 2: 1668: 1657: 1654: 1652: 1649: 1648: 1646: 1631: 1628: 1626: 1623: 1621: 1618: 1617: 1615: 1613: 1609: 1603: 1600: 1598: 1595: 1593: 1590: 1588: 1585: 1583: 1580: 1578: 1575: 1573: 1570: 1569: 1567: 1565: 1560: 1554: 1551: 1549: 1546: 1544: 1541: 1540: 1538: 1536: 1531: 1527: 1523: 1519: 1512: 1507: 1505: 1500: 1498: 1493: 1492: 1489: 1482: 1478: 1475: 1472: 1469: 1466: 1463: 1460: 1457: 1453: 1450: 1447: 1444: 1441: 1440: 1427: 1423: 1419: 1415: 1411: 1407: 1400: 1392: 1386: 1382: 1377: 1376: 1367: 1359: 1355: 1350: 1345: 1341: 1337: 1333: 1326: 1318: 1314: 1309: 1304: 1300: 1296: 1292: 1285: 1277: 1273: 1268: 1263: 1259: 1255: 1251: 1244: 1236: 1232: 1227: 1222: 1217: 1212: 1208: 1204: 1200: 1196: 1192: 1185: 1177: 1173: 1168: 1163: 1158: 1153: 1149: 1145: 1141: 1134: 1126: 1122: 1118: 1114: 1111:(11): 661–9. 1110: 1106: 1099: 1091: 1087: 1082: 1077: 1072: 1067: 1063: 1059: 1055: 1051: 1047: 1040: 1038: 1029: 1025: 1020: 1015: 1010: 1005: 1001: 997: 993: 986: 978: 974: 969: 964: 960: 956: 952: 948: 944: 940: 936: 929: 915:on 2016-05-25 914: 910: 903: 895: 891: 886: 881: 876: 871: 867: 863: 859: 852: 844: 840: 836: 832: 828: 824: 817: 811: 806: 798: 794: 790: 786: 782: 778: 774: 770: 763: 755: 751: 746: 741: 737: 733: 730:(5): 443–54. 729: 725: 721: 714: 706: 702: 698: 694: 690: 686: 682: 678: 674: 670: 663: 655: 651: 647: 643: 639: 635: 631: 627: 620: 614: 606: 602: 598: 594: 589: 584: 581:(2): 244–54. 580: 576: 572: 565: 557: 553: 549: 545: 541: 537: 533: 529: 522: 516: 508: 504: 499: 494: 490: 486: 482: 478: 474: 467: 459: 455: 451: 447: 443: 439: 436:(4): 233–45. 435: 431: 424: 422: 420: 415: 405: 402: 400: 397: 395: 392: 390: 387: 385: 382: 380: 377: 375: 372: 370: 369:Chimeric gene 367: 366: 360: 358: 357: 352: 348: 344: 340: 336: 331: 321: 319: 318:transcriptome 308: 306: 302: 298: 294: 290: 286: 283: 273: 270: 259: 257: 253: 249: 245: 241: 240:hybridization 239: 236:fluorescence 233: 223: 219: 217: 213: 209: 205: 201: 197: 193: 188: 186: 182: 178: 174: 170: 166: 162: 158: 154: 150: 146: 142: 138: 127: 125: 121: 117: 113: 109: 105: 101: 97: 93: 89: 85: 81: 67: 63: 61: 57: 53: 49: 45: 44:translocation 41: 37: 33: 19: 1625:Reassortment 1586: 1572:Transfection 1548:Transduction 1462:ChimerDB 2.0 1409: 1406:Biochemistry 1405: 1399: 1374: 1366: 1342:(1): S24-8. 1339: 1335: 1325: 1298: 1294: 1284: 1257: 1253: 1243: 1198: 1194: 1184: 1147: 1143: 1133: 1108: 1104: 1098: 1053: 1049: 999: 995: 985: 942: 938: 928: 917:. 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In 1973, 36:fusion gene 18:Gene fusion 1645:Categories 1602:Transposon 1564:eukaryotes 1562:Occurs in 1533:Primarily 919:2014-09-13 410:References 347:microscopy 305:Eukaryotes 88:chromosome 868:(1): 11. 351:expressed 311:Detection 262:Evolution 200:lymphomas 181:BCAM-AKT2 137:oncogenes 130:Oncogenes 56:neoplasia 1651:Mutation 1518:Genetics 1477:Archived 1452:Archived 1358:23036331 1317:32748425 1276:16601004 1235:11438739 1176:11820254 1125:11672867 1090:18949021 1028:19152679 977:19136943 894:21261984 843:12946230 797:40770452 789:17425505 754:20478527 705:85788789 697:16254181 654:17739576 605:46435450 597:19921709 556:17739576 507:19233641 458:26093482 450:17361217 363:See also 301:Bacteria 218:events. 192:promoter 173:sarcomas 124:chimeric 32:genetics 1336:Methods 1203:Bibcode 1081:2557144 1058:Bibcode 1019:2633275 968:2725402 947:Bibcode 885:3041646 745:2874722 677:Bibcode 669:Science 634:Bibcode 626:Science 536:Bibcode 528:Science 498:2676581 297:Archaea 289:guanine 285:adenine 282:purines 248:genomes 238:in situ 157:TMPRSS2 145:BCR-ABL 74:History 1468:dbCRID 1449:ChiPPI 1424:  1387:  1383:–534. 1356:  1315:  1274:  1233:  1223:  1174:  1164:  1123:  1088:  1078:  1026:  1016:  975:  965:  939:Nature 892:  882:  841:  795:  787:  752:  742:  703:  695:  652:  603:  595:  554:  505:  495:  456:  448:  343:tissue 175:, and 153:M2 AML 141:cancer 60:marker 1612:Viral 1426:28749 1226:35447 1167:65099 1002:: 5. 793:S2CID 701:S2CID 622:(PDF) 601:S2CID 524:(PDF) 454:S2CID 339:cells 50:, or 1422:PMID 1385:ISBN 1354:PMID 1313:PMID 1272:PMID 1231:PMID 1172:PMID 1121:PMID 1086:PMID 1024:PMID 973:PMID 890:PMID 839:PMID 785:PMID 750:PMID 693:PMID 650:PMID 593:PMID 552:PMID 503:PMID 446:PMID 303:and 287:and 280:The 116:ABL1 106:and 82:and 40:gene 34:, a 1414:doi 1381:533 1344:doi 1303:doi 1262:doi 1221:PMC 1211:doi 1162:PMC 1152:doi 1113:doi 1076:PMC 1066:doi 1014:PMC 1004:doi 963:PMC 955:doi 943:458 880:PMC 870:doi 831:doi 827:127 777:doi 740:PMC 732:doi 685:doi 673:310 642:doi 630:132 583:doi 579:220 544:doi 532:132 493:PMC 485:doi 438:doi 341:or 214:or 161:ERG 149:ALL 120:BCR 30:In 1647:: 1524:/ 1520:: 1420:. 1410:17 1408:. 1352:. 1340:59 1338:. 1334:. 1311:. 1299:98 1297:. 1293:. 1270:. 1258:22 1256:. 1252:. 1229:. 1219:. 1209:. 1199:98 1197:. 1193:. 1170:. 1160:. 1146:. 1142:. 1119:. 1109:17 1107:. 1084:. 1074:. 1064:. 1052:. 1048:. 1036:^ 1022:. 1012:. 998:. 994:. 971:. 961:. 953:. 941:. 937:. 888:. 878:. 864:. 860:. 837:. 825:. 791:. 783:. 773:12 771:. 748:. 738:. 728:17 726:. 722:. 699:. 691:. 683:. 671:. 648:. 640:. 628:. 624:. 599:. 591:. 577:. 573:. 550:. 542:. 530:. 526:. 501:. 491:. 481:19 479:. 475:. 452:. 444:. 432:. 418:^ 359:. 299:, 234:, 187:. 179:. 171:, 108:22 62:. 46:, 1510:e 1503:t 1496:v 1428:. 1416:: 1393:. 1360:. 1346:: 1319:. 1305:: 1278:. 1264:: 1237:. 1213:: 1205:: 1178:. 1154:: 1148:2 1127:. 1115:: 1092:. 1068:: 1060:: 1054:4 1030:. 1006:: 1000:8 979:. 957:: 949:: 922:. 896:. 872:: 866:4 845:. 833:: 799:. 779:: 756:. 734:: 707:. 687:: 679:: 656:. 644:: 636:: 607:. 585:: 558:. 546:: 538:: 509:. 487:: 460:. 440:: 434:7 159:- 104:9 20:)

Index

Gene fusion
genetics
gene
translocation
interstitial deletion
chromosomal inversion
neoplasia
marker

Peter Nowell
David Hungerford
chromosome
chronic myeloid leukemia
Philadelphia chromosome
Janet Rowley
9
22
chromosome translocation
chimeric
oncogenes
cancer
BCR-ABL
ALL
M2 AML
TMPRSS2
ERG
chromosome 21
hematological cancers
sarcomas
prostate cancer

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