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患者整个癌症病程中的基因组测序
Genome Sequencing during a Patient’s Journey through Cancer


Jyoti Nangalia ... 肿瘤 • 2019.11.28
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• 广泛的基因组测序对非小细胞肺癌是否有预后价值

癌症所起源的体细胞克隆摆脱了控制健康细胞功能的固有约束,因此发生了不受控制的增殖、组织浸润、免疫逃避和局部组织微环境重塑1。上述许多细胞特性是由癌症克隆在一生中累积的体细胞突变所引起。现代DNA测序方法已经能够以前所未有的规模对癌症进行完整的基因组特征鉴定,这最初使我们更好地理解了癌症生物学,最近又进入了临床应用。其中包括改进癌症的诊断和预后、发现新的治疗靶点、为治疗方案的选择提供决策支持以及在疾病监测中的应用。这篇综述探讨了我们在癌症基因组的系统性测序中学到的知识。本文讨论了基因组测序的当前临床应用和未来潜在的临床应用,并思考了将基因组测序大规模整合入癌症精准医学的前景和挑战(见视频)。

也称为“新一代测序”的大规模平行DNA测序方法可同时分析数百万DNA片段。我们可以将患者的肿瘤样本与同一患者的正常组织样本(通常是血液)一起测序,从而识别出遗传变异体,并将其归类为仅见于肿瘤样本的体细胞突变或也见于正常组织样本的遗传(生殖细胞系)多态性。原理验证研究表明,在识别出癌症克隆所获得的全部体细胞突变方面,具有可行性2-4。这些研究之后是对数万患者进行的数据分析5,我们因此更广泛地了解了癌症生物学(图1)。

 

图1. 从癌症基因组研究获得的知识

对患者癌症进行的测序使我们获得了多方面的肿瘤生物学知识。其中包括因癌症克隆的体细胞改变所获得的特征,如驱动突变、大规模染色体异常和免疫系统可识别的突变(新抗原)。此外也可评估遗传因素,如家族性癌症风险和影响癌症治疗药物代谢的变异体。

 

临床上最初实施的大规模平行测序通常是所谓的靶向测序,即选择出已知会导致癌症的300~600个基因或占基因组大约1%的所有蛋白质编码基因。靶向测序的主要优势是成本较低,以及在已知对癌症生物学最为重要的基因组特定区域进行较深入分析。然而,随着测序成本的进一步降低,对基因组全部30亿碱基对进行测序可能会成为标准操作,因为这样有可能识别出基因组所有区域内的所有类型突变6





作者信息

Jyoti Nangalia, Ph.D., and Peter J. Campbell, Ph.D.
From the Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, and Wellcome–MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research, the Department of Haematology, University of Cambridge, and the Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge — all in the United Kingdom. Address reprint requests to Dr. Campbell at the Wellcome Sanger Institute, Hinxton, CB10 1SA, United Kingdom, or at pc8@sanger.ac.uk.

 

参考文献

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-674.

2. Pleasance ED, Stephens PJ, O’Meara S, et al. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 2010;463:184-190.

3. Pleasance ED, Cheetham RK, Stephens PJ, et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010;463:191-196.

4. Ley TJ, Mardis ER, Ding L, et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 2008;456:66-72.

5. Ding L, Bailey MH, Porta-Pardo E, et al. Perspective on oncogenic processes at the end of the beginning of cancer genomics. Cell 2018;173(2):305.e10-320.e10.

6. Spencer DH, Ley TJ. Sequencing of tumor DNA to guide cancer risk assessment and therapy. JAMA 2018;319:1497-1498.

7. Bailey MH, Tokheim C, Porta-Pardo E, et al. Comprehensive characterization of cancer driver genes and mutations. Cell 2018;173(2):371.e18-385.e18.

8. Martincorena I, Raine KM, Gerstung M, et al. Universal patterns of selection in cancer and somatic tissues. Cell 2017;171(5):1029.e21-1041.e21.

9. Lawrence MS, Stojanov P, Mermel CH, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 2014;505:495-501.

10. Rubio-Perez C, Tamborero D, Schroeder MP, et al. In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities. Cancer Cell 2015;27:382-396.

11. Davoli T, Xu AW, Mengwasser KE, et al. Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome. Cell 2013;155:948-962.

12. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science 2013;339:957-959.

13. Horn S, Figl A, Rachakonda PS, et al. TERT promoter mutations in familial and sporadic melanoma. Science 2013;339:959-961.

14. Puente XS, Beà S, Valdés-Mas R, et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature 2015;526:519-524.

15. Fredriksson NJ, Ny L, Nilsson JA, Larsson E. Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types. Nat Genet 2014;46:1258-1263.

16. Rheinbay E, Parasuraman P, Grimsby J, et al. Recurrent and functional regulatory mutations in breast cancer. Nature 2017;547:55-60.

17. Sabarinathan R, Pich O, Martincorena I, et al. The whole-genome panorama of cancer drivers. bioRxiv. September 20, 2017 (https://www.biorxiv.org/content/10.1101/190330v1. opens in new tab).

18. Rheinbay E, Nielsen MM, Abascal F, et al. Discovery and characterization of coding and non-coding driver mutations in more than 2,500 whole cancer genomes. bioRxiv. December 23, 2017 (https://www.biorxiv.org/content/10.1101/237313v1. opens in new tab).

19. Zack TI, Schumacher SE, Carter SL, et al. Pan-cancer patterns of somatic copy number alteration. Nat Genet 2013;45:1134-1140.

20. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004.

21. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507-2516.

22. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non–small-cell lung cancer. N Engl J Med 2005;353:123-132.

23. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005;366:1527-1537.

24. Shaw AT, Kim D-W, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385-2394.

25. Viani GA, Afonso SL, Stefano EJ, De Fendi LI, Soares FV. Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer 2007;7:153-153.

26. Tomasetti C, Marchionni L, Nowak MA, Parmigiani G, Vogelstein B. Only three driver gene mutations are required for the development of lung and colorectal cancers. Proc Natl Acad Sci U S A 2015;112:118-123.

27. Welch JS, Ley TJ, Link DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell 2012;150:264-278.

28. Pfeifer GP, Denissenko MF, Olivier M, Tretyakova N, Hecht SS, Hainaut P. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 2002;21:7435-7451.

29. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature 2013;500:415-421.

30. Imielinski M, Berger AH, Hammerman PS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150:1107-1120.

31. Letouzé E, Shinde J, Renault V, et al. Mutational signatures reveal the dynamic interplay of risk factors and cellular processes during liver tumorigenesis. Nat Commun 2017;8:1315-1315.

32. Besaratinia A, Synold TW, Xi B, Pfeifer GP. G-to-T transversions and small tandem base deletions are the hallmark of mutations induced by ultraviolet a radiation in mammalian cells. Biochemistry 2004;43:8169-8177.

33. Davies H, Glodzik D, Morganella S, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med 2017;23:517-525.

34. Polak P, Kim J, Braunstein LZ, et al. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat Genet 2017;49:1476-1486.

35. Stephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 2011;144:27-40.

36. Baca SC, Prandi D, Lawrence MS, et al. Punctuated evolution of prostate cancer genomes. Cell 2013;153:666-677.

37. Papaemmanuil E, Rapado I, Li Y, et al. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Nat Genet 2014;46:116-125.

38. Lee E, Iskow R, Yang L, et al. Landscape of somatic retrotransposition in human cancers. Science 2012;337:967-971.

39. Tubio JMC, Li Y, Ju YS, et al. Mobile DNA in cancer: extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes. Science 2014;345:1251343-1251343.

40. Menghi F, Barthel FP, Yadav V, et al. The tandem duplicator phenotype is a prevalent genome-wide cancer configuration driven by distinct gene mutations. Cancer Cell 2018;34(2):197.e5-210.e5.

41. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-2520.

42. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434:917-921.

43. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:2495-2505.

44. Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019;381:317-327.

45. Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377:523-533.

46. Waddell N, Pajic M, Patch AM, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015;518:495-501.

47. Nik-Zainal S, Van Loo P, Wedge DC, et al. The life history of 21 breast cancers. Cell 2012;149:994-1007.

48. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366:883-892.

49. Campbell PJ, Yachida S, Mudie LJ, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 2010;467:1109-1113.

50. Shah SP, Morin RD, Khattra J, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 2009;461:809-813.

51. Ding L, Ley TJ, Larson DE, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012;481:506-510.

52. Mitchell TJ, Turajlic S, Rowan A, et al. Timing the landmark events in the evolution of clear cell renal cell cancer: TRACERx renal. Cell 2018;173(3):611.e17-623.e17.

53. Turajlic S, Xu H, Litchfield K, et al. Tracking cancer evolution reveals constrained routes to metastases: TRACERx renal. Cell 2018;173(3):581.e12-594.e12.

54. Turajlic S, Xu H, Litchfield K, et al. Deterministic evolutionary trajectories influence primary tumor growth: TRACERx renal. Cell 2018;173(3):595.e11-610.e11.

55. Cross W, Kovac M, Mustonen V, et al. The evolutionary landscape of colorectal tumorigenesis. Nat Ecol Evol 2018;2:1661-1672.

56. Sottoriva A, Kang H, Ma Z, et al. A Big Bang model of human colorectal tumor growth. Nat Genet 2015;47:209-216.

57. Yates LR, Gerstung M, Knappskog S, et al. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Nat Med 2015;21:751-759.

58. Gao R, Davis A, McDonald TO, et al. Punctuated copy number evolution and clonal stasis in triple-negative breast cancer. Nat Genet 2016;48:1119-1130.

59. Jamal-Hanjani M, Wilson GA, McGranahan N, et al. Tracking the evolution of non–small-cell lung cancer. N Engl J Med 2017;376:2109-2121.

60. de Bruin EC, McGranahan N, Mitter R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 2014;346:251-256.

61. Brastianos PK, Carter SL, Santagata S, et al. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov 2015;5:1164-1177.

62. Yates LR, Knappskog S, Wedge D, et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 2017;32(2):169.e7-184.e7.

63. Ding L, Ellis MJ, Li S, et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 2010;464:999-1005.

64. Landau DA, Carter SL, Stojanov P, et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 2013;152:714-726.

65. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209-2221.

66. Diaz LA Jr, Williams RT, Wu J, et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012;486:537-540.

67. Murtaza M, Dawson SJ, Tsui DWY, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013;497:108-112.

68. Wong TN, Ramsingh G, Young AL, et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature 2015;518:552-555.

69. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-128.

70. McGranahan N, Rosenthal R, Hiley CT, et al. Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 2017;171(6):1259.e11-1271.e11.

71. McGranahan N, Furness AJS, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016;351:1463-1469.

72. Brown CE, Alizadeh D, Starr R, et al. Regression of glioblastoma after chimeric antigen receptor t-cell therapy. N Engl J Med 2016;375:2561-2569.

73. Keskin DB, Anandappa AJ, Sun J, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 2019;565:234-239.

74. Rahman N. Realizing the promise of cancer predisposition genes. Nature 2014;505:302-308.

75. Ong KR, Woodward ER, Killick P, Lim C, Macdonald F, Maher ER. Genotype-phenotype correlations in von Hippel-Lindau disease. Hum Mutat 2007;28:143-149.

76. Huang K-L, Mashl RJ, Wu Y, et al. Pathogenic germline variants in 10,389 adult cancers. Cell 2018;173(2):355.e14-370.e14.

77. Michailidou K, Lindström S, Dennis J, et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017;551:92-94.

78. Schumacher FR, Al Olama AA, Berndt SI, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet 2018;50:928-936.

79. Wellmann R, Borden BA, Danahey K, et al. Analyzing the clinical actionability of germline pharmacogenomic findings in oncology. Cancer 2018;124:3052-3065.

80. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616-1622.

81. Villani A, Shore A, Wasserman JD, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol 2016;17:1295-1305.

82. Kucab JE, Zou X, Morganella S, et al. A compendium of mutational signatures of environmental agents. Cell 2019;177(4):821.e16-836.e16.

83. Rosenquist TA, Grollman AP. Mutational signature of aristolochic acid: clue to the recognition of a global disease. DNA Repair (Amst) 2016;44:205-211.

84. Scelo G, Riazalhosseini Y, Greger L, et al. Variation in genomic landscape of clear cell renal cell carcinoma across Europe. Nat Commun 2014;5:5135-5135.

85. Poon SL, Pang S-T, McPherson JR, et al. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Sci Transl Med 2013;5:197ra101-197ra101.

86. Hoang ML, Chen CH, Sidorenko VS, et al. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med 2013;5:197ra102-197ra102.

87. Totoki Y, Tatsuno K, Covington KR, et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat Genet 2014;46:1267-1273.

88. Teixeira VH, Pipinikas CP, Pennycuick A, et al. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat Med 2019;25:517-525.

89. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014;371:2488-2498.

90. Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 2014;371:2477-2487.

91. Xie M, Lu C, Wang J, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 2014;20:1472-1478.

92. Young AL, Challen GA, Birmann BM, Druley TE. Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nat Commun 2016;7:12484-12484.

93. Abelson S, Collord G, Ng SWK, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 2018;559:400-404.

94. Ross-Innes CS, Becq J, Warren A, et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma. Nat Genet 2015;47:1038-1046.

95. Boutros PC, Fraser M, Harding NJ, et al. Spatial genomic heterogeneity within localized, multifocal prostate cancer. Nat Genet 2015;47:736-745.

96. Vannucchi AM, Barbui T, Cervantes F, et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26:Suppl 5:v85-v99.

97. Steward DL, Carty SE, Sippel RS, et al. Performance of a multigene genomic classifier in thyroid nodules with indeterminate cytology: a prospective blinded multicenter study. JAMA Oncol 2019;5:204-212.

98. Ross JS, Wang K, Gay L, et al. Comprehensive genomic profiling of carcinoma of unknown primary site: new routes to targeted therapies. JAMA Oncol 2015;1:40-49.

99. Jiao W, Polak P, Karlic R, et al. Accurate discrimination of 23 major cancer types via whole genome somatic mutation patterns. bioRxiv. November 14, 2017 (https://www.biorxiv.org/content/10.1101/214494v2. opens in new tab).

100. Mina M, Raynaud F, Tavernari D, et al. Conditional selection of genomic alterations dictates cancer evolution and oncogenic dependencies. Cancer Cell 2017;32(2):155.e6-168.e6.

101. Grinfeld J, Nangalia J, Baxter EJ, et al. Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med 2018;379:1416-1430.

102. Curtis C, Shah SP, Chin S-F, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012;486:346-352.

103. Rueda OM, Sammut SJ, Seoane JA, et al. Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups. Nature 2019;567:399-404.

104. Northcott PA, Buchhalter I, Morrissy AS, et al. The whole-genome landscape of medulloblastoma subtypes. Nature 2017;547:311-317.

105. Joensuu H, Kellokumpu-Lehtinen P-L, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 2006;354:809-820.

106. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 2013;369:111-121.

107. Gerstung M, Papaemmanuil E, Martincorena I, et al. Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nat Genet 2017;49:332-340.

108. Papaemmanuil E, Cazzola M, Boultwood J, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011;365:1384-1395.

109. Kawaguchi Y, Kopetz S, Newhook TE, et al. Mutation status of RAS, TP53, and SMAD4 is superior to mutation status of RAS alone for predicting prognosis after resection of colorectal liver metastases. Clin Cancer Res 2019;25:5843-5851.

110. Lundberg P, Karow A, Nienhold R, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood 2014;123:2220-2228.

111. Hieronymus H, Schultz N, Gopalan A, et al. Copy number alteration burden predicts prostate cancer relapse. Proc Natl Acad Sci U S A 2014;111:11139-11144.

112. Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science 2017;355:eaaf8399-eaaf8399.

113. O’Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 2007;110:2242-2249.

114. Van Allen EM, Wagle N, Sucker A, et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014;4:94-109.

115. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008;359:1757-1765.

116. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-1043.

117. Sharma SV, Lee DY, Li B, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 2010;141:69-80.

118. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014;371:1877-1888.

119. Hmeljak J, Sanchez-Vega F, Hoadley KA, et al. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov 2018;8:1548-1565.

120. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 2013;499:43-49.

121. Iorio F, Knijnenburg TA, Vis DJ, et al. A landscape of pharmacogenomic interactions in cancer. Cell 2016;166:740-754.

122. Behan FM, Iorio F, Picco G, et al. Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens. Nature 2019;568:511-516.

123. Chan EM, Shibue T, McFarland JM, et al. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature 2019;568:551-556.

124. Chen AP, Eljanne M, Harris L, Malik S, Seibel NL. National Cancer Institute Basket/Umbrella clinical trials: MATCH, LungMAP, and beyond. Cancer J 2019;25:272-281.

125. Jhaveri KL, Wang XV, Makker V, et al. Ado-trastuzumab emtansine (T-DM1) in patients with HER2 amplified tumors excluding breast and gastric/gastro-esophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH Trial (EAY131) sub-protocol Q. Ann Oncol 2019 August 27 (Epub ahead of print).

126. Aggarwal C, Redman MW, Lara PN Jr, et al. SWOG S1400D (NCT02965378. opens in new tab), a Phase II study of the fibroblast growth factor receptor inhibitor AZD4547 in previously treated patients with fibroblast growth factor pathway-activated stage IV squamous cell lung cancer (Lung-MAP substudy). J Thorac Oncol 2019;14:1847-1852.

127. Edelman MJ, Redman MW, Albain KS, et al. SWOG S1400C (NCT02154490. opens in new tab) — a phase II study of palbociclib for previously treated cell cycle gene alteration-positive patients with stage IV squamous cell lung cancer (Lung-MAP substudy). J Thorac Oncol 2019;14:1853-1859.

128. Langer CJ, Redman MW, Wade JL, et al. SWOG S1400B (NCT02785913. opens in new tab), a phase II study of GDC-0032 (taselisib) for previously treated PI3K-positive patients with stage IV squamous cell lung cancer (Lung-MAP sub-study). J Thorac Oncol 2019;14:1839-1846.

129. Yung TK, Chan KC, Mok TS, Tong J, To KF, Lo YM. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res 2009;15:2076-2084.

130. Nawroz H, Koch W, Anker P, Stroun M, Sidransky D. Microsatellite alterations in serum DNA of head and neck cancer patients. Nat Med 1996;2:1035-1037.

131. Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008;14:985-990.

132. Dawson S-J, Tsui DWY, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 2013;368:1199-1209.

133. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 2017;545:446-451.

134. Leary RJ, Kinde I, Diehl F, et al. Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med 2010;2:20ra14-20ra14.

135. McBride DJ, Orpana AK, Sotiriou C, et al. Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors. Genes Chromosomes Cancer 2010;49:1062-1069.

136. Flohr T, Schrauder A, Cazzaniga G, et al. Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia 2008;22:771-782.

137. Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev 2006;20:29-41.

138. Alioto TS, Buchhalter I, Derdak S, et al. A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nat Commun 2015;6:10001-10001.

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