Tumour Heterogeneity and Evolutionary Dynamics in Colorectal Cancer

Overview

Journal Oncogenesis

Date 2021 Jul 17

PMID 34272358

Citations 15

Authors

Dedrick Kok Hong Chan

Simon James Alexander Buczacki

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) has a global burden of disease. Our current understanding of CRC has progressed from initial discoveries which focused on the stepwise accumulation of key driver mutations, as encapsulated in the Vogelstein model, to one in which marked heterogeneity leads to a complex interplay between clonal populations. Current evidence suggests that an initial explosion, or "Big Bang", of genetic diversity is followed by a period of neutral dynamics. A thorough understanding of this interplay between clonal populations during neutral evolution gives insights into the roles in which driver genes may participate in the progress from normal colonic epithelium to adenoma and carcinoma. Recent advances have focused not only on genetics, transcriptomics, and proteomics but have also investigated the ecological and evolutionary processes which transform normal cells into cancer. This review first describes the role which driver mutations play in the Vogelstein model and subsequently demonstrates the evidence which supports a more complex model. This article also aims to underscore the significance of tumour heterogeneity and diverse clonal populations in cancer progression.

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References

Gessani S, Belardelli F . Immune Dysfunctions and Immunotherapy in Colorectal Cancer: The Role of Dendritic Cells. Cancers (Basel). 2019; 11(10). PMC: 6827143. DOI: 10.3390/cancers11101491. View

Speetjens F, Kuppen P, Morreau H, van der Burg S . Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology. 2008; 135(2):711-2. DOI: 10.1053/j.gastro.2008.04.040. View

Minussi D, Nicholson M, Ye H, Davis A, Wang K, Baker T . Breast tumours maintain a reservoir of subclonal diversity during expansion. Nature. 2021; 592(7853):302-308. PMC: 8049101. DOI: 10.1038/s41586-021-03357-x. View

Ling S, Hu Z, Yang Z, Yang F, Li Y, Lin P . Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution. Proc Natl Acad Sci U S A. 2015; 112(47):E6496-505. PMC: 4664355. DOI: 10.1073/pnas.1519556112. View

Galdiero M, Bianchi P, Grizzi F, Caro G, Basso G, Ponzetta A . Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer. Int J Cancer. 2016; 139(2):446-56. DOI: 10.1002/ijc.30076. View

Nagtegaal I, Odze R, Klimstra D, Paradis V, Rugge M, Schirmacher P . The 2019 WHO classification of tumours of the digestive system. Histopathology. 2019; 76(2):182-188. PMC: 7003895. DOI: 10.1111/his.13975. View

Colom B, Alcolea M, Piedrafita G, Hall M, Wabik A, Dentro S . Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium. Nat Genet. 2020; 52(6):604-614. PMC: 7116672. DOI: 10.1038/s41588-020-0624-3. View

Sottoriva A, Kang H, Ma Z, Graham T, Salomon M, Zhao J . A Big Bang model of human colorectal tumor growth. Nat Genet. 2015; 47(3):209-16. PMC: 4575589. DOI: 10.1038/ng.3214. View

Bond C, Liu C, Kawamata F, McKeone D, Fernando W, Jamieson S . Oncogenic BRAF mutation induces DNA methylation changes in a murine model for human serrated colorectal neoplasia. Epigenetics. 2017; 13(1):40-48. PMC: 5836984. DOI: 10.1080/15592294.2017.1411446. View

10.

Lim J, Thiery J . Alternative path to EMT: regulation of apicobasal polarity in Drosophila. Dev Cell. 2011; 21(6):983-4. DOI: 10.1016/j.devcel.2011.11.017. View

11.

Diepenbruck M, Waldmeier L, Ivanek R, Berninger P, Arnold P, van Nimwegen E . Tead2 expression levels control the subcellular distribution of Yap and Taz, zyxin expression and epithelial-mesenchymal transition. J Cell Sci. 2014; 127(Pt 7):1523-36. DOI: 10.1242/jcs.139865. View

12.

Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A . VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003; 161(6):1163-77. PMC: 2172999. DOI: 10.1083/jcb.200302047. View

13.

Fang M, Ou J, Hutchinson L, Green M . The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG Island Methylator phenotype. Mol Cell. 2014; 55(6):904-915. PMC: 4170521. DOI: 10.1016/j.molcel.2014.08.010. View

14.

Lee-Six H, Olafsson S, Ellis P, Osborne R, Sanders M, Moore L . The landscape of somatic mutation in normal colorectal epithelial cells. Nature. 2019; 574(7779):532-537. DOI: 10.1038/s41586-019-1672-7. View

15.

Guinney J, Dienstmann R, Wang X, De Reynies A, Schlicker A, Soneson C . The consensus molecular subtypes of colorectal cancer. Nat Med. 2015; 21(11):1350-6. PMC: 4636487. DOI: 10.1038/nm.3967. View

16.

Inda M, Bonavia R, Mukasa A, Narita Y, Sah D, Vandenberg S . Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev. 2010; 24(16):1731-45. PMC: 2922502. DOI: 10.1101/gad.1890510. View

17.

Ouahoud S, Voorneveld P, van der Burg L, de Jonge-Muller E, Schoonderwoerd M, Paauwe M . Bidirectional tumor/stroma crosstalk promotes metastasis in mesenchymal colorectal cancer. Oncogene. 2020; 39(12):2453-2466. DOI: 10.1038/s41388-020-1157-z. View

18.

Salazar R, Roepman P, Capella G, Moreno V, Simon I, Dreezen C . Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol. 2010; 29(1):17-24. DOI: 10.1200/JCO.2010.30.1077. View

19.

Umar A, Risinger J, Hawk E, Barrett J . Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer. 2004; 4(2):153-8. DOI: 10.1038/nrc1278. View

20.

Andre T, Shiu K, Kim T, Jensen B, Jensen L, Punt C . Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020; 383(23):2207-2218. DOI: 10.1056/NEJMoa2017699. View