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Tumour heterogeneity information


Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential.[1] This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity). A minimal level of intra-tumour heterogeneity is a simple consequence of the imperfection of DNA replication: whenever a cell (normal or cancerous) divides, a few mutations are acquired[2]—leading to a diverse population of cancer cells.[3] The heterogeneity of cancer cells introduces significant challenges in designing effective treatment strategies. However, research into understanding and characterizing heterogeneity can allow for a better understanding of the causes and progression of disease. In turn, this has the potential to guide the creation of more refined treatment strategies that incorporate knowledge of heterogeneity to yield higher efficacy.[4]

Tumour heterogeneity has been observed in leukemias,[5] breast,[6] prostate,[7][8][9] colon,[10][11][12] brain,[13] esophagus,[14] head and neck,[15] bladder[16] and gynecological carcinomas,[17] liposarcoma,[18] and multiple myeloma.[19]

  1. ^ Marusyk, A; Polyak, K (2010). "Tumor heterogeneity: Causes and consequences". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1805 (1): 105–117. doi:10.1016/j.bbcan.2009.11.002. PMC 2814927. PMID 19931353.
  2. ^ Vogelstein, Bert; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A.; Kinzler, K.W. (2013). "Cancer Genome Landscapes". Science. 373 (6127): 1546–1556. Bibcode:2013Sci...339.1546V. doi:10.1126/science.1235122. PMC 3749880. PMID 23539594.
  3. ^ Heppner, G.A. (1984). "Tumor Heterogeneity". Cancer Research. 44 (6): 2259–2265. PMID 6372991.
  4. ^ Reiter, Johannes G; Makohon-Moore, Alvin P; Gerold, Jeffrey M; Heyde, Alexander; Attiyeh, Marc A; Kohutek, Zachary A; Tokheim, Collin J; Brown, Alexia; DeBlasio, Rayne; Niyazov, Juliana; Zucker, Amanda; Karchin, Rachel; Kinzler, Kenneth W; Iacobuzio-Donahue, Christine A; Vogelstein, Bert; Nowak, Martin A (2018). "Minimal functional driver gene heterogeneity among untreated metastases". Science. 361 (6406): 1033–1037. Bibcode:2018Sci...361.1033R. doi:10.1126/science.aat7171. PMC 6329287. PMID 30190408.
  5. ^ Campbell, P. J.; Pleasance, E. D.; Stephens, P. J.; Dicks, E; Rance, R; Goodhead, I; Follows, G. A.; Green, A. R.; Futreal, P. A.; Stratton, M. R. (2008). "Subclonal phylogenetic structures in cancer revealed by ultra-deep sequencing". Proceedings of the National Academy of Sciences. 105 (35): 13081–13086. Bibcode:2008PNAS..10513081C. doi:10.1073/pnas.0801523105. PMC 2529122. PMID 18723673.
  6. ^ Shipitsin, M; Campbell, L. L.; Argani, P; Weremowicz, S; Bloushtain-Qimron, N; Yao, J; Nikolskaya, T; Serebryiskaya, T; Beroukhim, R; Hu, M; Halushka, M. K.; Sukumar, S; Parker, L. M.; Anderson, K. S.; Harris, L. N.; Garber, J. E.; Richardson, A. L.; Schnitt, S. J.; Nikolsky, Y; Gelman, R. S.; Polyak, K (2007). "Molecular definition of breast tumor heterogeneity". Cancer Cell. 11 (3): 259–273. doi:10.1016/j.ccr.2007.01.013. PMID 17349583.
  7. ^ MacIntosh, C. A.; Stower, M; Reid, N; Maitland, N. J. (1998). "Precise microdissection of human prostate cancers reveals genotypic heterogeneity". Cancer Research. 58 (1): 23–28. PMID 9426051.
  8. ^ Alvarado, C; Beitel, L. K.; Sircar, K; Aprikian, A; Trifiro, M; Gottlieb, B (2005). "Somatic mosaicism and cancer: A micro-genetic examination into the role of the androgen receptor gene in prostate cancer". Cancer Research. 65 (18): 8514–8518. doi:10.1158/0008-5472.CAN-05-0399. PMID 16166332.
  9. ^ Konishi, N; Hiasa, Y; Matsuda, H; Tao, M; Tsuzuki, T; Hayashi, I; Kitahori, Y; Shiraishi, T; Yatani, R; Shimazaki, J (1995). "Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma". The American Journal of Pathology. 147 (4): 1112–1122. PMC 1871010. PMID 7573356.
  10. ^ González-García, I; Solé, R. V.; Costa, J (2002). "Metapopulation dynamics and spatial heterogeneity in cancer". Proceedings of the National Academy of Sciences. 99 (20): 13085–13089. Bibcode:2002PNAS...9913085G. doi:10.1073/pnas.202139299. PMC 130590. PMID 12351679.
  11. ^ Samowitz, W. S.; Slattery, M. L. (1999). "Regional reproducibility of microsatellite instability in sporadic colorectal cancer". Genes, Chromosomes and Cancer. 26 (2): 106–114. doi:10.1002/(SICI)1098-2264(199910)26:2<106::AID-GCC2>3.0.CO;2-F. PMID 10469448. S2CID 5643190.
  12. ^ Giaretti, W; Monaco, R; Pujic, N; Rapallo, A; Nigro, S; Geido, E (1996). "Intratumor heterogeneity of K-ras2 mutations in colorectal adenocarcinomas: Association with degree of DNA aneuploidy". The American Journal of Pathology. 149 (1): 237–245. PMC 1865212. PMID 8686748.
  13. ^ Heppner, G. H. (1984). "Tumor heterogeneity". Cancer Research. 44 (6): 2259–2265. PMID 6372991.
  14. ^ Maley, C. C.; Galipeau, P. C.; Finley, J. C.; Wongsurawat, V. J.; Li, X; Sanchez, C. A.; Paulson, T. G.; Blount, P. L.; Risques, R. A.; Rabinovitch, P. S.; Reid, B. J. (2006). "Genetic clonal diversity predicts progression to esophageal adenocarcinoma". Nature Genetics. 38 (4): 468–473. doi:10.1038/ng1768. PMID 16565718. S2CID 1898396.
  15. ^ Califano, J; Van Der Riet, P; Westra, W; Nawroz, H; Clayman, G; Piantadosi, S; Corio, R; Lee, D; Greenberg, B; Koch, W; Sidransky, D (1996). "Genetic progression model for head and neck cancer: Implications for field cancerization". Cancer Research. 56 (11): 2488–2492. PMID 8653682.
  16. ^ Sauter, G; Moch, H; Gasser, T. C.; Mihatsch, M. J.; Waldman, F. M. (1995). "Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and metastatic bladder cancer". Cytometry. 21 (1): 40–46. doi:10.1002/cyto.990210109. PMID 8529469.
  17. ^ Fujii, H; Yoshida, M; Gong, Z. X.; Matsumoto, T; Hamano, Y; Fukunaga, M; Hruban, R. H.; Gabrielson, E; Shirai, T (2000). "Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity". Cancer Research. 60 (1): 114–120. PMID 10646862.
  18. ^ Horvai, A. E.; Devries, S; Roy, R; O'Donnell, R. J.; Waldman, F (2009). "Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma". Modern Pathology. 22 (11): 1477–1488. doi:10.1038/modpathol.2009.119. PMID 19734852.
  19. ^ Pantou, D; Rizou, H; Tsarouha, H; Pouli, A; Papanastasiou, K; Stamatellou, M; Trangas, T; Pandis, N; Bardi, G (2005). "Cytogenetic manifestations of multiple myeloma heterogeneity". Genes, Chromosomes and Cancer. 42 (1): 44–57. doi:10.1002/gcc.20114. PMID 15495197. S2CID 43218546.

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