Will we cure cancer by sequencing thousands of genomes?

Molecular Cytogenetics

Joshua M Nicholson¹ 

[1] Virginia Tech, Department of Biological Sciences, 1981 Kraft Dr, Blacksburg, VA 24060, USA

关键词: Tumor suppressor genes;    Oncogenes;    Karyotype;    Cancer;    Cancer genome;   

Others  :  1150523
DOI  :  10.1186/1755-8166-6-57

 received in 2013-09-04, accepted in 2013-11-06,  发布年份 2013

【 摘 要 】

The promise to understand cancer and develop efficacious therapies by sequencing thousands of cancers has not occurred. Mutations in specific genes termed oncogenes and tumor suppressor genes are extremely heterogeneous amongst the same type of cancer as well as between cancers. They provide little selective advantage to the cancer and in functional tests have yet to be shown to be sufficient for transformation. Here I discuss the karyotyptic theory of cancer and ask if it is time for a new approach to understanding and ultimately treating cancer.

【 授权许可】

   
2013 Nicholson; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Miklos GLG: The human cancer genome project – one more misstep in the war on cancer. Nat Biotechnol 2005, 23:535-537.
• [2]Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, et al.: The genomic landscapes of human breast and colorectal cancers. Science 2007, 318(5853):1108-1113.
• [3]Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, et al.: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 2008, 456(7218):66-72.
• [4]Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA, et al.: Characterizing the cancer genome in lung adenocarcinoma. Nature 2007, 450(7171):893-898.
• [5]Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al.: The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314(5797):268-274.
• [6]Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, et al.: An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321(5897):1807-1812.
• [7]Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, et al.: Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009, 361(11):1058-1066.
• [8]Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, et al.: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012, 366(10):883-892.
• [9]Salk JJ, Fox EJ, Loeb LA: Mutational heterogeneity in human cancers: origin and consequences. Annu Rev Pathol 2010, 5:51-75.
• [10]Bozic I, Antal T, Ohtsuki H, Carter H, Kim D, Chen S, Karchin R, Kinzler KW, Vogelstein B, Nowak MA: Accumulation of driver and passenger mutations during tumor progression. Proc Natl Acad Sci U S A 2010, 107(43):18545-18550.
• [11]Denko NC, Giaccia AJ, Stringer JR, Stambrook PJ: The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. Proc Natl Acad Sci U S A 1994, 91(11):5124-5128.
• [12]Rubin H, Xu K: Evidence for the progressive and adaptive nature of spontaneous transformation in the NIH/3T3 cell line. Proc Natl Acad Sci U S A 1989, 86(6):1860-1864.
• [13]Gilbert PX, Harris H: The role of the ras oncogene in the formation of tumours. J Cell Sci 1988, 90(Pt 3):433-446.
• [14]Greig RG, Koestler TP, Trainer DL, Corwin SP, Miles L, Kline T, Sweet R, Yokoyama S, Poste G: Tumorigenic and metastatic properties of “normal” and ras-transfected NIH/3 T3 cells. Proc Natl Acad Sci U S A 1985, 82(11):3698-3701.
• [15]Boone CW, Jacobs JB: Sarcomas routinely produced from putatively nontumorigenic Balb/3T3 and C3H/10/T1/2 cells by subcutaneous inoculation attached to plastic platelets. J Supramol Struct 1976, 5(2):131-137.
• [16]Stratton MR: Exploring the Genomes of Cancer Cells: Progress and Promise. Science 2011, 331(6024):1553-1558.
• [17]Stepanenko AA, Kavsan VM: Immortalization and malignant transformation of eukaryotic cells. TSitologiia i genetika 2012, 46(2):36-75.
• [18]Hua VY, Wang WK, Duesberg PH: Dominant transformation by mutated human ras genes in vitro requires more than 100 times higher expression than is observed in cancers. Proc Natl Acad Sci U S A 1997, 94(18):9614-9619.
• [19]Li R, Rasnick D, Duesberg P, Zimonjic D, et al.: Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res 2001, 61:8838-8844. Cancer Res 2002, 62(21):6345–6348; discussion 6348–6349
• [20]Nicholson JM, Duesberg P: On the karyotypic origin and evolution of cancer cells. Cancer Genet Cytogenet 2009, 194(2):96-110.
• [21]Li L, McCormack AA, Nicholson JM, Fabarius A, Hehlmann R, Sachs RK, Duesberg PH: Cancer-causing karyotypes: chromosomal equilibria between destabilizing aneuploidy and stabilizing selection for oncogenic function. Cancer Genet Cytogenet 2009, 188(1):1-25.
• [22]Klein A, Li N, Nicholson JM, McCormack AA, Graessmann A, Duesberg P: Transgenic oncogenes induce oncogene-independent cancers with individual karyotypes and phenotypes. Cancer Genet Cytogenet 2010, 200(2):79-99.
• [23]Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, et al.: Signatures of mutational processes in human cancer. Nature 2013, 500(7463):415-421.
• [24]Schulze S, Petersen I: Gender and ploidy in cancer survival. Cell Oncol (Dordr) 2011, 34(3):199-208.
• [25]Mitelman F, Johansson B, Mertens F: Mitelman Database of Chromosome Aberrations in Cancer 2011. 2011. http://cgap.nci.nih.gov/Chromosomes/Mitelman webcite
• [26]Gebhart E, Liehr T: Patterns of genomic imbalances in human solid tumors. Int J Oncol 2000, 16:383-399.
• [27]Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, et al.: The landscape of somatic copy-number alteration across human cancers. Nature 2010, 463(7283):899-905.
• [28]Nicholson JM, Cimini D: Cancer karyotypes: survival of the fittest. Frontiers in oncology 2013, 3:1-19.
• [29]Baudis M: Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data. BMC Cancer 2007, 7:226. BioMed Central Full Text
• [30]Duesberg P, Mandrioli D, McCormack A, Nicholson JM: Is carcinogenesis a form of speciation? Cell Cycle 2011, 10(13):2100-2114.
• [31]Vincent MD: Cancer: beyond speciation. In Advances in cancer research. Edited by David G. MA: Academic Press; 2011:283-350. Volume 112
• [32]Heng HH, Stevens JB, Bremer SW, Ye KJ, Liu G, Ye CJ: The evolutionary mechanism of cancer. J Cell Biochem 2010, 109(6):1072-1084.
• [33]Duesberg P: Chromosomal chaos and cancer. Sci Am 2007, 296(5):52-59.
• [34]Duesberg P, Rasnick D, Li R, Winters L, Rausch C, Hehlmann R: How aneuploidy may cause cancer and genetic instability. Anticancer Res 1999, 19(6A):4887-4906.
• [35]Boveri T: Zur Frage der Entstehung maligner Tumoren. Jena, Germany: Gustav Fischer Verlag; 1914.
• [36]Boveri T, Harris H: Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci 2008, 121(Supplement 1):1-84.
• [37]Lengauer C, Kinzler KW, Vogelstein B: Genetic instability in colorectal cancers. Nature 1997, 386:623-627.
• [38]Duijf PH, Schultz N, Benezra R: Cancer cells preferentially lose small chromosomes. Int J Cancer 2012, 132(10):2316-2326.
• [39]Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR: A census of human cancer genes. Nat Rev Cancer 2004, 4(3):177-183.
• [40]Upender MB, Habermann JK, McShane LM, Korn EL, Barrett JC, Difilippantonio MJ, Ried T: Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells. Cancer Res 2004, 64(19):6941-6949.
• [41]Shapiro BL: Down syndrome - a disruption of homeostasis. Am J Med Genet 1983, 14:241-269.