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Chapter 3  Genomic Approaches to Hematology  35


            signatures are based on relative transcript abundance (as opposed to,   Cheung HW, Cowley GS, Weir BA, et al: Systematic investigation of genetic
            for example, genome sequencing), it is subject to technical variation   vulnerabilities across cancer cell lines reveals lineage-specific dependencies
            such  as  stromal  admixture  of  tumors  that  can  distort  a  diagnostic   in ovarian cancer. Proc Natl Acad Sci USA 108:12372, 2011.
            signature. Third, although the academic publishing system tends to   Cong L, Ran FA, Cox D, et al: Multiplex genome engineering using CRISPR/
            reward initial discoveries (which are often published in high-profile   Cas systems. Science 339:819–823, 2013.
            journals), the essential follow-up validation studies tend to be valued   Dryja TP, Cavenee W, White R, et al: Homozygosity of chromosome 13 in
            less, and therefore investigators do not have an incentive to follow up   retinoblastoma. N Engl J Med 310:550, 1984.
            on  their  initial  observations.  Fourth,  the  economics  of  molecular   Du  J,  Bernansconi  P,  Clauser  KR,  et al:  Bead-based  profiling  of  tyrosine
            diagnostics  have  in  general  not  been  favorable,  thus  discouraging   kinase phosphorylation identifies SRC as a potential target for glioblas-
            companies  from  making  major  investments  in  the  validation  and   toma therapy. Nat Biotechnol 27:77, 2009.
            commercialization  of  promising  diagnostic  tests.  It  is  likely  that   Emmert-Buck MR, Bonner RF, Smith PD, et al: Laser capture microdissec-
            diagnostic tests will command more of a premium in the future as a   tion. Science 274:998, 1996.
            mechanism to use expensive therapeutics only in patients likely to   Garraway  LA,  Lander  ES:  Lessons  from  the  cancer  genome.  Cell  153:17,
            benefit, but the time required for this to evolve is uncertain.  2013.
              However, the potential utility of clinically relevant gene expression   Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell
            signatures has regained interest with the progress and greater avail-  144:646, 2011.
            ability of sophisticated RNA sequencing technology. Whether RNA   Hoshida Y, Villanueva A, Kobayashi M, et al: Gene expression in fixed tissues
            sequencing  provides  data  sufficiently  robust  to  be  used  in  clinical   and outcome in hepatocellular carcinoma. N Engl J Med 359:1995, 2008.
            routine remains to be established.                    Jaiswal S, Fontanillas P, Flannick J, et al: Age-related clonal hematopoiesis
                                                                    associated with adverse outcomes. N Engl J Med 371:2488, 2014.
                                                                  Jinek M, Chylinski K, Fonfara I, et al: A programmable dual-RNA-guided
            FUTURE DIRECTIONS                                       DNA endonuclease in adaptive bacterial immunity. Science 337:816–821,
                                                                    2012.
            The field of genomics has matured greatly over the past decade. Major   Johannessen CM, Boehm JS, Kim SY, et al: COT drives resistance to RAF
            analytical  advances  have  made  it  possible  to  analyze  and  interpret   inhibition through MAP kinase pathway reactivation. Nature 468:968,
            complex datasets beyond what was previously possible. In addition,   2010.
            dropping costs have made it possible to generate data at a scale that   Lohr  JG,  Kim  S,  Gould  J,  et al:  Genetic  interrogation  of  circulating
            was  never  before  imaginable.  DNA  sequencing  is  now  routine  at   multiple myeloma cells at single-cell resolution. Sci Transl Med 8:363ra147,
            many academic centers and is increasingly being used to drive preci-  2016.
            sion medicine by suggesting potential therapies based on individual   Lohr JG, Adalsteinsson VA, Cibulskis K, et al: Whole-exome sequencing of
            patients’ genetic profiles. Nevertheless, such approaches are still in   circulating tumor cells provides a window into metastatic prostate cancer.
            their infancy; the majority of patients do not receive direct benefit   Nat Biotechnol 32:479, 2014.
            from such precision medicine approaches. The future will also hold   Macosko EZ, Basu A, Satija R, et al: Highly parallel genome-wide expression
            an explosion of functional genomic studies, particularly using genome   profiling of individual cells using nanoliter droplets. Cell 161:1202, 2015.
            editing methods such as CRISPR/Cas9. With deep genomic, tran-  Mardis  ER,  Ding  L,  Dooling  DJ,  et al:  Recurring  mutations  found  by
            scriptomic, and epigenetic data already available for the most common   sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058,
            hematologic and malignant diseases, and with new data being gener-  2009.
            ated at an ever-increasing rate, there will be great opportunity for   Melo SA, Luecke LB, Kahlert C, et al: Glypican-1 identifies cancer exosomes
            diagnostic and therapeutic development. The integration of genomic   and detects early pancreatic cancer. Nature 523:177, 2015.
            and  other  high-throughput  sequencing  approaches  into  clinical   Miyamoto DT, Zheng Y, Wittner BS, et al: RNA-Seq of single prostate CTCs
            research  and  routine  clinical  care  will  continue  to  be  one  of  the   implicates noncanonical Wnt signaling in antiandrogen resistance. Science
            greatest  challenges  and  opportunities  in  medicine  in  the  decade   349:1351, 2015.
            ahead.                                                Morin  RD,  Mendez-Lago  M,  Mungall  AJ,  et al:  Frequent  mutation  of
                                                                    histone-modifying genes in non-Hodgkin lymphoma. Nature 476:298,
                                                                    2011.
            SUGGESTED READINGS                                    Nik-Zainal  S,  van  Loo  P,  Wedge  DC,  et al: The  life  history  of  21  breast
                                                                    cancers. Cell 149:994, 2012.
            Alizadeh AA, Eisen MB, Davis RE, et al: Distinct types of diffuse large B-cell   Paiva  B,  Vidriales  MB,  Cerveró  J,  et al:  Multiparameter  flow  cytometric
              lymphoma identified by gene expression profiling. Nature 403:503, 2000.  remission  is  the  most  relevant  prognostic  factor  for  multiple  myeloma
            Armstrong SA, Staunton JE, Silverman LB, et al: MLL translocations specify   patients  who  undergo  autologous  stem  cell  transplantation.  Blood
              a distinct gene expression profile that distinguishes a unique leukemia.   112:4017, 2008.
              Nat Genet 30:41, 2002.                              Paweletz CP, Charboneau L, Bichsel VE, et al: Reverse phase protein microar-
            Bernstein BE, Kamal M, Lindblad-Toh K, et al: Genomic maps and com-  rays  which  capture  disease  progression  show  activation  of  pro-survival
              parative  analysis  of  histone  modifications  in  human  and  mouse.  Cell   pathways at the cancer invasion front. Oncogene 20:1981, 2001.
              120:169, 2005.                                      Ramsköld D, Luo S, Wang YC, et al: Full-length mRNA-Seq from single-cell
            Beroukhim  R,  Getz  G,  Nghiemphu  L,  et al:  Assessing  the  significance  of   levels  of  RNA  and  individual  circulating  tumor  cells.  Nat  Biotechnol
              chromosomal  aberrations  in  cancer:  methodology  and  application  to   30:777, 2012.
              glioma. Proc Natl Acad Sci USA 104:20007, 2007.     Robinson  JT, Thorvaldsdóttir  H,  Winckler  W,  et al:  Integrative  genomics
            Boyd  SD,  Marshall  EL,  Merker  JD,  et al:  Measurement  and  clinical   viewer. Nat Biotechnol 29:24, 2011.
              monitoring  of  human  lymphocyte  clonality  by  massively  parallel  VDJ   Rowley JD: The critical role of chromosome translocations in human leuke-
              pyrosequencing. Sci Transl Med 1:12ra23, 2009.        mias. Annu Rev Genet 32:495, 1998.
            Buenrostro  JD,  Giresi  PG,  Zaba  LC,  et al:  Transposition  of  native  chro-  Satija R, Farrell JA, Gennert D, et al: Spatial reconstruction of single-cell gene
              matin  for  fast  and  sensitive  epigenomic  profiling  of  open  chromatin,   expression data. Nat Biotech 33:495–502, 2015.
              DNA-binding proteins and nucleosome position. Nat Methods 10:1213,   Schwarzenbach H, Hoon DSB, Pantel K: Cell-free nucleic acids as biomark-
              2013.                                                 ers in cancer patients. Nat Rev Cancer 11:426, 2011.
            Cabili  MN,  Trapnell  C,  Goff  L,  et al:  Integrative  annotation  of  human   Shaffer AL, Emre NC, Lamy L, et al: IRF4 addiction in multiple myeloma.
              large intergenic noncoding RNAs reveals global properties and specific   Nature 454:226, 2008.
              subclasses. Genes Dev 25:1915, 2011.                Shipp MA, Ross KN, Tamayo P, et al: Diffuse large B-cell lymphoma outcome
            Carter SL, Cibulskis K, Helman E, et al: Absolute quantification of somatic   prediction by gene-expression profiling and supervised machine learning.
              DNA alterations in human cancer. Nat Biotechnol 30:413, 2012.  Nat Med 8:68, 2002.
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