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Author |
Tomasetti, C.; Vogelstein, B. |
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Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions |
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Journal Article |
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Year |
2015 |
Publication |
Science (New York, N.Y.) |
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Science |
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347 |
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6217 |
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78-81 |
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Abstract |
Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. |
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Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA. ctomasetti@jhu.edu vogelbe@jhmi.edu |
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0036-8075 |
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PMID:25554788 |
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CBM.UAM @ ccobaleda @ |
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538 |
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Author |
Bateman, C.M.; Alpar, D.; Ford, A.M.; Colman, S.M.; Wren, D.; Morgan, M.; Kearney, L.; Greaves, M. |
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Title |
Evolutionary trajectories of hyperdiploid ALL in monozygotic twins |
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Journal Article |
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Year |
2015 |
Publication |
Leukemia |
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Leukemia |
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29 |
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1 |
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58-65 |
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Identical twins have provided unique insights on timing or sequence of genetic events in acute lymphoblastic leukaemia (ALL). To date, this has mainly focused on ALL with MLL or ETV6-RUNX1 fusions, with hyperdiploid ALL remaining less well characterised. We examined three pairs of monozygotic twins, two concordant and one discordant for hyperdiploid ALL, for single-nucleotide polymorphism (SNP)-defined copy number alterations (CNAs), IGH/L plus TCR gene rearrangements and mutations in NRAS, KRAS, FLT3 and PTPN11 genes. We performed whole exome sequencing in one concordant twin pair. Potential 'driver' CNAs were low, 0-3 per case, and all were different within a pair. One patient had an NRAS mutation that was lacking from leukaemic cells of the twin sibling. By exome sequencing, there were 12 nonsynonymous mutations found in one twin and 5 in the other, one of which in SCL44A2 was shared or identical. Concordant pairs had some identical IGH/L and TCR rearrangements. In the twin pair with discordant hyperdiploid ALL, the healthy co-twin had persistent low level hyperdiploid CD19+ cells that lacked a CNA present in the ALL cells of her sibling. From these data, we propose that hyperdiploid ALL arises in a pre-B cell in utero and mutational changes necessary for clinical ALL accumulate subclonally and postnatally. |
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Centre for Evolution and Cancer, The Institute of Cancer Research, Sutton, UK |
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0887-6924 |
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PMID:24897505 |
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CBM.UAM @ ccobaleda @ |
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544 |
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Glushkova, O.V.; Khrenov, M.O.; Novoselova, T.V.; Lunin, S.M.; Parfenyuk, S.B.; Alekseev, S.I.; Fesenko, E.E.; Novoselova, E.G. |
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The role of the NF-κB, SAPK/JNK, and TLR4 signalling pathways in the responses of RAW 264.7 cells to extremely low-intensity microwaves |
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Journal Article |
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2015 |
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International Journal of Radiation Biology |
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1-8 |
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WP5 In vitro |
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UNIBAS @ david.schuermann @ |
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615 |
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Hou, Q.; Wang, M.; Wu, S.; Ma, X.; An, G.; Liu, H.; Xie, F. |
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Oxidative changes and apoptosis induced by 1800-MHz electromagnetic radiation in NIH/3T3 cells |
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Journal Article |
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2015 |
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Electromagnetic Biology and Medicine |
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34 |
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85-92 |
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1800-mhz; apoptosis; dna damage; mobile; phone radiation; ros |
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UNIBAS @ david.schuermann @ |
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620 |
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Barteri, M.; De Carolis, R.; Marinelli, F.; Tomassetti, G.; Montemiglio, L.C. |
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Effects of microwaves (900 MHz) on peroxidase systems: a comparison between lactoperoxidase and horseradish peroxidase |
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Journal Article |
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Year |
2015 |
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Electromagnetic Biology and Medicine |
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00 |
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00 |
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1-7 |
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900 mhz; 900 MHz; electromagneti fields; enzyme kinetics; horseradish peroxidase; lactoperoxidase; microwaves; radiofrequency; peroxidase; enzyme; kinetics |
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Informa Healthcare USA, Inc |
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UNIBAS @ david.schuermann @ |
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630 |
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