298:
254:
246:
637:
Shipitsin, M.; Willson, J. K. V.; Sukumar, S.; Polyak, K.; Park, B. H.; Pethiyagoda, C. L.; Pant, P. V. K.; Ballinger, D. G.; Sparks, A. B.; Hartigan, J.; Smith, D. R.; Suh, E.; Papadopoulos, N.; Buckhaults, P.; Markowitz, S. D.; Parmigiani, G.; Kinzler, K. W.; Velculescu, V. E.; Vogelstein, B. (2007). "The
Genomic Landscapes of Human Breast and Colorectal Cancers".
262:
degradation technique. Following these landmark papers, over 20 years later ‘Second
Generation’ high-throughput next generation sequencing (HT-NGS) was born followed by ‘Third Generation HT-NGS technology’ in 2010. The figures to the right illustrate the general biological pipeline and companies involved in second and third generation HT-NGS sequencing.
326:
shared mutations amongst tumors, cluster around known oncogenes, and are tend to be non-silent. Passenger mutations, which are not important in the progression of the disease, are randomly distributed throughout the genome. It has been estimated that the average tumor carries c.a. 80 somatic mutations, fewer than 15 of which are expected to be drivers.
329:
A personal-genomics analysis requires further functional characterization of the detected mutant genes, and the development of a basic model of the origin and progression of the tumor. This analysis can be used to make pharmacological treatment recommendations. As of
February 2012, this has only been
325:
A major goal of cancer genome sequencing is to identify driver mutations: genetic changes which increase the mutation rate in the cell, leading to more rapid tumor evolution and metastasis. It is difficult to determine driver mutations from DNA sequence alone; but drivers tend to be the most commonly
316:
Since even non-cancerous cells accumulate somatic mutations, it is necessary to compare sequence of the tumor to a matched normal tissue in order to discover which mutations are unique to the cancer. In some cancers, such as leukemia, it is not practical to match the cancer sample to a normal tissue,
76:
The first report of cancer genome sequencing appeared in 2006. In this study 13,023 genes were sequenced in 11 breast and 11 colorectal tumors. A subsequent follow up was published in 2007 where the same group added just over 5,000 more genes and almost 8,000 transcript species to complete the exomes
223:
The TCGA is a multi-institutional effort to understand the molecular basis of cancer through genome analysis technologies, including large-scale genome sequencing techniques. Hundreds of samples are being collected, sequenced and analyzed. Currently the cancer tissue being collected include: central
350:
Cancer genome sequencing can be used to provide clinically relevant information in patients with rare or novel tumor types. Translating sequence information into a clinical treatment plan is highly complicated, requires experts of many different fields, and is not guaranteed to lead to an effective
104:
The Cancer Genome
Anatomy Project (CGAP) was first funded in 1997 with the goal of documenting the sequences of RNA transcripts in tumor cells. As technology improved, the CGAP expanded its goals to include the determination of gene expression profiles of cancerous, precancerous and normal tissues.
576:
Sjoblom, T.; Jones, S.; Wood, L. D.; Parsons, D. W.; Lin, J.; Barber, T. D.; Mandelker, D.; Leary, R. J.; Ptak, J.; Silliman, N.; Szabo, S.; Buckhaults, P.; Farrell, C.; Meeh, P.; Markowitz, S. D.; Willis, J.; Dawson, D.; Willson, J. K. V.; Gazdar, A. F.; Hartigan, J.; Wu, L.; Liu, C.; Parmigiani,
338:
A large-scale screen for somatic mutations in breast and colorectal tumors showed that many low-frequency mutations each make small contribution to cell survival. If cell survival is determined by many mutations of small effect, it is unlikely that genome sequencing will uncover a single "Achilles
320:
It has been estimated that discovery of all somatic mutations in a tumor would require 30-fold sequencing coverage of the tumor genome and a matched normal tissue. By comparison, the original draft of the human genome had approximately 65-fold coverage. To facilitate further improvement in somatic
636:
Wood, L. D.; Parsons, D. W.; Jones, S.; Lin, J.; Sjoblom, T.; Leary, R. J.; Shen, D.; Boca, S. M.; Barber, T.; Ptak, J.; Silliman, N.; Szabo, S.; Dezso, Z.; Ustyanksky, V.; Nikolskaya, T.; Nikolsky, Y.; Karchin, R.; Wilson, P. A.; Kaminker, J. S.; Zhang, Z.; Croshaw, R.; Willis, J.; Dawson, D.;
261:
Cancer genome sequencing utilizes the same technology involved in whole genome sequencing. The history of sequencing has come a long way, originating in 1977 by two independent groups - Fredrick Sanger’s enzymatic didoxy DNA sequencing technique and the Allen Maxam and Walter
Gilbert chemical
210:
The Cancer Genome
Projects goal is to identify sequence variants and mutations critical in the development of human cancers. The project involves the systematic screening of coding genes and flanking splice junctions of all genes in the human genome for acquired mutations in human cancers. To
161:
The power of cancer genome sequencing lies in the heterogeneity of cancers and patients. Most cancers have a variety of subtypes and combined with these ‘cancer variants’ are the differences between a cancer subtype in one individual and in another individual. Cancer genome sequencing allows
227:
The components of the TCGA research network include: Biospecimen Core
Resources, Genome Characterization Centers, Genome Sequencing Centers, Proteome Characterization Centers, a Data Coordinating Center, and Genome Data Analysis Centers. Each cancer type will undergo comprehensive genomic
34:’s WG sequencing projects, saliva, epithelial cells or bone - cancer genome sequencing involves direct sequencing of primary tumor tissue, adjacent or distal normal tissue, the tumor micro environment such as fibroblast/stromal cells, or metastatic tumor sites.
346:
Clinically significant properties of tumors, including drug resistance, are sometimes caused by large-scale rearrangements of the genome, rather than single mutations. In this case, information about single nucleotide variants will be of limited utility.
342:
Cancers are heterogeneous populations of cells. When sequence data is derived from a whole tumor, information about the differences in sequence and expression pattern between cells is lost. This difficulty can be ameliorated by single-cell analysis.
321:
mutation detection in cancer, the
Sequencing Quality Control Phase 2 Consortium has established a pair of tumor-normal cell lines as community reference samples and data sets for the benchmarking of cancer mutation detections.
37:
Similar to whole genome sequencing, the information generated from this technique include: identification of nucleotide bases (DNA or RNA), copy number and sequence variants, mutation status, and structural changes such as
211:
investigate these events, the discovery sample set will include DNA from primary tumor, normal tissue (from the same individuals) and cancer cell lines. All results from this project are amalgamated and stored within the
236:
The ICGC’s goal is “To obtain a comprehensive description of genomic, transcriptomic and epigenomic changes in 50 different tumor types and/or subtypes which are of clinical and societal importance across the globe”.
181:
These cellular factions could only have been identified through cancer genome sequencing, showing the information that sequencing can yield, and the complexity and heterogeneity of a tumor within one individual.
367:, which designates tumors and growths detected on whole-body imaging by coincidence). The detection of such variants may result in additional measures such as further testing or lifestyle management.
162:
clinicians and oncologists to identify the specific and unique changes a patient has undergone to develop their cancer. Based on these changes, a personalized therapeutic strategy can be undertaken.
122:, first funded in 2005, focuses on DNA sequencing. It has published a census of genes causally implicated in cancer, and a number of whole-genome resequencing screens for genes implicated in cancer.
178:
et al. identified cellular fractions characterized by common mutational changes to illustrate the heterogeneity of a particular tumor pre- and post-treatment vs. normal blood in one individual.
23:
of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s).
577:
G.; Park, B. H.; Bachman, K. E.; Papadopoulos, N.; Vogelstein, B.; Kinzler, K. W.; Velculescu, V. E. (2006). "The
Consensus Coding Sequences of Human Breast and Colorectal Cancers".
339:
heel" target for anti-cancer drugs. However, somatic mutations tend to cluster in a limited number of signalling pathways, which are potential treatment targets.
202:(a larger organization) is a voluntary scientific organization that provides a forum for collaboration among the world's leading cancer and genomic researchers.
141:
data from many different research groups. As of
December 2011, the ICGC includes 45 committed projects and has data from 2,961 cancer genomes available.
2201:
77:
of 11 breast and colorectal tumors. The first whole cancer genome to be sequenced was from cytogenetically normal acute myeloid leukaemia by Ley
2125:"Aneuploidy approaching a perfect score in predicting and preventing cancer: highlights from a conference held in Oakland, CA in January, 2004"
411:
199:
126:
451:
278:
158:
changes. Identification and characterization of all these changes can be accomplished through various cancer genome sequencing strategies.
309:
to form a representation of the chromosomes being sequenced. With cancer genomes, this is usually done by aligning the reads to the human
101:
Historically, cancer genome sequencing efforts has been divided between transcriptome-based sequencing projects and DNA-centered efforts.
2222:
198:
funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). Combined with these efforts, the
1866:"Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing"
170:
A big contribution to cancer death and failed cancer treatment is clonal evolution at the cytogenetic level, for example as seen in
116:
228:
characterization and analysis. The data and information generated is freely available through the projects TCGA data portal.
190:
The two main projects focused on complete cancer characterization in individuals, heavily involving sequencing include the
1092:
416:
286:
154:
The process of tumorigenesis that transforms a normal cell to a cancerous cell involve a series of complex genetic and
1496:
Garson OM; et al. (July 1989). "Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse".
1076:
2237:
1118:
426:
39:
456:
2262:
363:
is the set of detected genomic variants not related to the cancer under study. (The term is a play on the name
2267:
406:
195:
171:
20:
1469:
Joseph R. Testa; et al. (September 1979). "Evolution of Karyotypes in Acute Nonlymphocytic Leukemia".
224:
nervous system, breast, gastrointestinal, gynecologic, head and neck, hematologic, thoracic, and urologic.
1976:
1959:
Wood, L.D.; et al. (November 2007). "The genomic landscapes of human breast and colorectal cancers".
654:
212:
109:
58:
396:
330:
done for patients clinical trials designed to assess the personal genomics approach to cancer treatment.
1821:
386:
191:
119:
2248:
Francis S. Collins and Anna D. Barker. "Mapping the Cancer Genome". Scientific American, February 2007
2167:
Kohane, I. S.; Masys, D. R.; Altman, R. B. (2006). "The Incidentalome: A Threat to Genomic Medicine".
297:
2033:
1968:
1776:
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1604:
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1182:
926:
779:
722:
646:
586:
540:
401:
381:
270:
70:
2080:
Miklos, G. L. (May 2005). "The human cancer genome project: one more misstep in the war on cancer".
1981:
659:
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282:
2105:
2002:
995:
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1513:
1478:
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1395:
1339:
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1249:
1208:
1055:"Cancer Genome Anatomy Project (CGAP) | Cancer Genome Characterization Initiative (CGCI)"
1036:
987:
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846:
797:
748:
680:
672:
610:
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730:
664:
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548:
499:
489:
310:
253:
245:
2232:
1536:"Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing"
1080:
768:"Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution"
306:
277:
sequencing technology. Three major third generation platforms include Pacific Biosciences
134:
62:
31:
27:
2022:"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses"
2037:
1972:
1931:
1914:
1780:
1667:
1608:
1551:
1186:
930:
783:
726:
650:
590:
544:
2054:
2021:
1890:
1865:
1797:
1764:
1735:
1710:
1568:
1535:
1446:
1421:
1390:
1364:"Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors"
1363:
1293:
1268:
1203:
1170:
947:
914:
890:
865:
841:
816:
743:
710:
706:
504:
477:
446:
266:
1686:
1651:
1627:
1592:
1244:
1227:
2256:
1509:
1422:"Personalized oncology through integrative high-throughput sequencing: a pilot study"
364:
54:
2109:
622:
2006:
999:
692:
431:
301:
The work-flow of the sequencing of a tumor from biopsy to treatment recommendation.
983:
1437:
494:
26:
Unlike whole genome (WG) sequencing which is typically from blood cells, such as
138:
43:
1881:
1284:
1726:
1031:
1014:
155:
49:
Cancer genome sequencing is not limited to WG sequencing and can also include
1380:
817:"A small-cell lung cancer genome with complex signatures of tobacco exposure"
676:
606:
2045:
1990:
1617:
668:
598:
2188:
2180:
2150:
2101:
2063:
1998:
1940:
1899:
1850:
1806:
1744:
1577:
1455:
1399:
1343:
1302:
1212:
1096:
1074:
970:
E Pinnisi (May 1997). "A catalog of cancer genes at the click of a mouse".
956:
899:
866:"A comprehensive catalogue of somatic mutations from a human cancer genome"
850:
801:
752:
711:"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome"
684:
614:
562:
529:"The complete genome of an individual by massively parallel DNA sequencing"
513:
215:. COSMIC also includes mutational data published in scientific literature.
1676:
1636:
1517:
1253:
1040:
991:
1695:
1482:
130:
2093:
1788:
1559:
1334:
1317:
1194:
938:
881:
832:
792:
767:
734:
553:
528:
2141:
2124:
175:
108:
The CGAP published the largest publicly available collection of cancer
81:
in November 2008. The first breast cancer tumor was sequenced by Shah
1841:
1122:
296:
252:
244:
129:(ICGC) was founded in 2007 with the goal of integrating available
66:
50:
1915:"Unraveling the genetics of cancer: genome sequencing and beyond"
2227:
1913:
Wong, K. M.; Hudson, T. J.; McPherson, J. D. (September 2011).
1119:"Cancer genome project (CGP) - Wellcome Trust Sanger Institute"
1763:
Straton, M. R.; Campbell, P. J.; Futreal, P.A. (April 2009).
85:
in October 2009, the first lung and skin tumors by Pleasance
1318:"The cancer epigenome--components and functional correlates"
2217:
1054:
915:"The genomic complexity of primary human prostate cancer"
305:
As with any genome sequencing project, the reads must be
89:
in January 2010, and the first prostate tumors by Berger
1415:
1413:
1411:
1409:
2242:
2202:
Cancer Gene Sequencing Raises New Medical Ethics Issues
1148:
1954:
1952:
1950:
1822:"Initial sequencing and analysis of the human genome"
1709:
Chandra Shekhar Pareek; et al. (November 2011).
1169:
International Cancer Genome Consortium (April 2010).
478:"The Diploid Genome Sequence of an Individual Human"
194:, based at the Wellcome Trust Sanger Institute and
1593:"DNA sequencing with chain-terminating inhibitors"
317:so a different non-cancerous tissue must be used.
1357:
1355:
1353:
1171:"International network of cancer genome projects"
1758:
1756:
1754:
913:Michael F. Berger; et al. (February 2011).
864:Erin D. Pleasance; et al. (December 2009).
815:Erin D. Pleasance; et al. (December 2009).
265:Three major second generation platforms include
1711:"Sequencing technologies and genome sequencing"
1591:Frederick Sanger; et al. (December 1977).
1420:Roychowdhury, S.; et al. (November 2011).
1226:Kenneth W Kinzler; et al. (October 1996).
1015:"Cancer genome anatomy project set for takeoff"
2162:
2160:
1650:Allan Maxam; Walter Gilbert (February 1977).
1316:Angela H. Ting; et al. (December 2006).
1267:Peter A. Jones; et al. (February 2007).
232:International Cancer Genome Consortium (ICGC)
8:
1919:Annual Review of Genomics and Human Genetics
1529:
1527:
766:Sohrab P. Shah; et al. (October 2009).
527:David A. Wheeler; et al. (April 2008).
174:(AML). In a Nature study published in 2011,
1820:Lander, E.S.; et al. (February 2001).
1228:"Lessons from Hereditary Colorectal Cancer"
1143:
1141:
1139:
279:Single Molecule Real Time (SMRT) sequencing
2075:
2073:
1864:Fang, L.T.; et al. (September 2021).
2140:
2053:
2020:Jones, S.; et al. (September 2008).
1980:
1930:
1889:
1840:
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1734:
1685:
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1626:
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1567:
1445:
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1202:
1030:
946:
889:
840:
791:
742:
658:
552:
503:
493:
476:Samuel Levy; et al. (October 2007).
1149:"International Cancer Genome Consortium"
1019:Journal of the National Cancer Institute
61:. These methods can be used to quantify
468:
2243:International Cancer Genome Consortium
1534:Ding, L.; et al. (January 2012).
412:International Cancer Genome Consortium
402:Center for Personalized Cancer Therapy
200:International Cancer Genome Consortium
127:International Cancer Genome Consortium
186:Comprehensive Cancer Genomic Projects
73:events in addition to sequence data.
7:
452:Single molecule real time sequencing
150:The Complexity and Biology of Cancer
1932:10.1146/annurev-genom-082509-141532
2123:Duesberg, P.; Rasnick, D. (2004).
1117:www-core (Web team) (2013-01-30).
14:
1652:"A new method for sequencing DNA"
1498:Cancer Genetics and Cytogenetics
1362:Jone, S.J.; et al. (2010).
377:454 Life Sciences Pyrosequencing
2204:by Janis C. Kelly. Sep 06, 2013
709:; et al. (November 2008).
275:Illumina’s bridge amplification
1426:Science Translational Medicine
1121:. Sanger.ac.uk. Archived from
1095:. Sanger.ac.uk. Archived from
219:The Cancer Genome Atlas (TCGA)
1:
1245:10.1016/S0092-8674(00)81333-1
984:10.1126/science.276.5315.1023
1510:10.1016/0165-4608(89)90024-1
1438:10.1126/scitranslmed.3003161
1093:"COSMIC: Cancer Gene census"
495:10.1371/journal.pbio.0050254
417:Ion semiconductor sequencing
287:Ion semiconductor sequencing
57:, micronome sequencing, and
1715:Journal of Applied Genetics
1269:"The Epigenomics of Cancer"
206:Cancer Genome Project (CGP)
2284:
1882:10.1038/s41587-021-00993-6
1285:10.1016/j.cell.2007.01.029
427:Next-generation sequencing
241:Technologies and platforms
40:chromosomal translocations
2218:The Cancer Genome Project
1727:10.1007/s13353-011-0057-x
1013:B Kuska (December 1996).
457:SNV calling from NGS data
267:Roche/454 Pyro-sequencing
257:3rd Generation Sequencing
249:2nd Generation Sequencing
69:expression, and identify
1381:10.1186/gb-2010-11-8-r82
17:Cancer genome sequencing
2228:The Cancer Genome Atlas
2046:10.1126/science.1164368
1991:10.1126/science.1145720
1618:10.1073/pnas.74.12.5463
1322:Genes & Development
1032:10.1093/jnci/88.24.1801
669:10.1126/science.1145720
599:10.1126/science.1133427
407:DNA nanoball sequencing
196:the Cancer Genome Atlas
172:acute myeloid leukaemia
110:expressed sequence tags
21:whole genome sequencing
2181:10.1001/jama.296.2.212
302:
258:
250:
213:COSMIC cancer database
59:end-sequence profiling
2238:Cancer Genome Project
2233:Cancer Genome Project
1677:10.1073/pnas.74.2.560
387:Cancer Genome Project
300:
256:
248:
192:Cancer Genome Project
120:Cancer Genome Project
2082:Nature Biotechnology
1870:Nature Biotechnology
1079:May 3, 2011, at the
382:ABI Solid Sequencing
271:ABI/SOLiD sequencing
71:alternative splicing
2094:10.1038/nbt0505-535
2038:2008Sci...321.1801J
1973:2007Sci...318.1108W
1789:10.1038/nature07943
1781:2009Natur.458..719S
1765:"The cancer genome"
1668:1977PNAS...74..560M
1609:1977PNAS...74.5463S
1560:10.1038/nature10738
1552:2012Natur.481..506D
1335:10.1101/gad.1464906
1195:10.1038/nature08987
1187:2010Natur.464..993T
939:10.1038/nature09744
931:2011Natur.470..214B
882:10.1038/nature08658
833:10.1038/nature08629
793:10.1038/nature08489
784:2009Natur.461..809S
735:10.1038/nature07485
727:2008Natur.456...66L
651:2007Sci...318.1108W
645:(5853): 1108–1113.
591:2006Sci...314..268S
554:10.1038/nature06884
545:2008Natur.452..872W
422:Nanopore sequencing
397:Caris Life Sciences
392:Cancer Genome Atlas
283:Nanopore sequencing
2142:10.4161/cc.3.6.938
1057:. Cgap.nci.nih.gov
442:Precision medicine
303:
259:
251:
166:Clinical Relevance
117:Sanger Institute's
93:in February 2011.
1835:(6822): 860–921.
1775:(7239): 719–724.
1432:(111): 111ra121.
585:(5797): 268–274.
437:Polony sequencing
273:by ligation, and
2275:
2205:
2199:
2193:
2192:
2164:
2155:
2154:
2144:
2120:
2114:
2113:
2077:
2068:
2067:
2057:
2032:(5897): 1801–6.
2017:
2011:
2010:
1984:
1956:
1945:
1944:
1934:
1910:
1904:
1903:
1893:
1876:(9): 1151–1160.
1861:
1855:
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1842:10.1038/35057062
1826:
1817:
1811:
1810:
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1679:
1647:
1641:
1640:
1630:
1620:
1588:
1582:
1581:
1571:
1546:(7382): 506–10.
1531:
1522:
1521:
1493:
1487:
1486:
1466:
1460:
1459:
1449:
1417:
1404:
1403:
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1063:
1062:
1051:
1045:
1044:
1034:
1010:
1004:
1003:
978:(5315): 1023–4.
967:
961:
960:
950:
925:(7333): 214–20.
910:
904:
903:
893:
861:
855:
854:
844:
827:(7278): 184–90.
812:
806:
805:
795:
778:(7265): 809–13.
763:
757:
756:
746:
703:
697:
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662:
633:
627:
626:
573:
567:
566:
556:
524:
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517:
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473:
351:treatment plan.
311:reference genome
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2273:
2272:
2263:Cancer genomics
2253:
2252:
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2158:
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2121:
2117:
2079:
2078:
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2019:
2018:
2014:
1982:10.1.1.218.5477
1958:
1957:
1948:
1912:
1911:
1907:
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1862:
1858:
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1819:
1818:
1814:
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1471:Cancer Research
1468:
1467:
1463:
1419:
1418:
1407:
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1360:
1351:
1328:(23): 3215–31.
1315:
1314:
1310:
1266:
1265:
1261:
1225:
1224:
1220:
1181:(7291): 993–8.
1168:
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1137:
1128:
1126:
1125:on July 2, 2013
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912:
911:
907:
876:(7278): 191–6.
863:
862:
858:
814:
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809:
765:
764:
760:
721:(7218): 66–72.
705:
704:
700:
660:10.1.1.218.5477
635:
634:
630:
575:
574:
570:
539:(7189): 872–6.
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145:Societal Impact
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63:gene expression
32:James D. Watson
28:J. Craig Venter
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11:
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2268:DNA sequencing
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1967:(5853): 8–9.
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1279:(4): 683–92.
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432:Oncogenomics
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707:Timothy Ley
334:Limitations
2257:Categories
2129:Cell Cycle
1925:: 407–30.
1374:(8): R82.
1155:2013-09-14
1151:. Icgc.org
1129:2013-09-14
1103:2013-09-14
1061:2013-09-14
463:References
156:epigenetic
139:epigenetic
1977:CiteSeerX
677:0036-8075
655:CiteSeerX
607:0036-8075
307:assembled
281:, Oxford
112:in 2003.
2189:16835427
2151:15197343
2110:39302093
2102:15877064
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1900:34504347
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1807:19360079
1745:21698376
1578:22237025
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1400:20696054
1344:17158741
1303:17320506
1213:20393554
1077:Archived
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900:20016485
851:20016488
802:19812674
753:18987736
685:17932254
623:10805017
615:16959974
563:18421352
514:17803354
371:See also
30:'s and
2055:2848990
2034:Bibcode
2026:Science
2007:7586573
1969:Bibcode
1961:Science
1891:8532138
1798:2821689
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1736:3189340
1664:Bibcode
1637:1422003
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891:3145108
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587:Bibcode
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505:1964779
131:genomic
97:History
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67:miRNA
51:exome
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2098:PMID
2060:PMID
1995:PMID
1937:PMID
1896:PMID
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1692:PMID
1656:PNAS
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1514:PMID
1479:PMID
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1273:Cell
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1232:Cell
1209:PMID
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