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Colorectal Cancer Subtypes – The Current Portrait

  • Peter JordanEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1110)

Abstract

Colorectal cancer (CRC) is one prominent example for how chemotherapy has been changing by moving from the use of general cytotoxic agents to more tumour-specific drugs. For example, antibody-based drugs neutralize a growth factor receptor protein on the surface of tumour cells. The development of such new therapeutic opportunities requires a more thorough and systematic subclassification of CRC because tumour cells can exploit several alternative genetic pathways for their survival. This chapter gives an overview on CRC subtypes as an introduction to the following book chapters that will describe aspects of specific subtypes, and how these may lead to the development of novel pathway-specific drugs for a more precise therapeutic intervention.

Keywords

Chromosomal instability Colorectal cancer subtype Consensus molecular subtype Microsatellite instability Oncogene Polyp Serrated pathway 

References

  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66:683–691.  https://doi.org/10.1136/gutjnl-2015-310912 CrossRefPubMedGoogle Scholar
  2. Bardelli A, Siena S (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28:1254–1261.  https://doi.org/10.1200/JCO.2009.24.6116 CrossRefPubMedGoogle Scholar
  3. Beach R, Chan AO-O, Wu T-T, White JA, Morris JS, Lunagomez S, Broaddus RR, Issa J-PJ, Hamilton SR, Rashid A (2005) BRAF mutations in aberrant crypt foci and hyperplastic polyposis. Am J Pathol 166:1069–1075.  https://doi.org/10.1016/S0002-9440(10)62327-9 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bettington M, Walker N, Clouston A, Brown I, Leggett B, Whitehall V (2013) The serrated pathway to colorectal carcinoma: current concepts and challenges. Histopathology 62:367–386.  https://doi.org/10.1111/his.12055 CrossRefPubMedGoogle Scholar
  5. Boparai KS, Dekker E, Polak MM, Musler AR, van Eeden S, van Noesel CJM (2011) A serrated colorectal cancer pathway predominates over the classic WNT pathway in patients with hyperplastic polyposis syndrome. Am J Pathol 178:2700–2707.  https://doi.org/10.1016/j.ajpath.2011.02.023 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Brenner H, Kloor M, Pox CP (2014) Colorectal cancer. Lancet 383:1490–1502.  https://doi.org/10.1016/S0140-6736(13)61649-9 CrossRefPubMedGoogle Scholar
  7. Budinska E, Popovici V, Tejpar S, D’Ario G, Lapique N, Sikora KO, Di Narzo AF, Yan P, Hodgson JG, Weinrich S, Bosman F, Roth A, Delorenzi M (2013) Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer: gene expression heterogeneity in colorectal cancer. J Pathol 231:63–76.  https://doi.org/10.1002/path.4212 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DVF, Byrom D, Cortina C, Morral C, Barceló C, Tosi S, Riera A, Attolini CS-O, Rossell D, Sancho E, Batlle E (2015) Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 47:320–329.  https://doi.org/10.1038/ng.3225 CrossRefPubMedGoogle Scholar
  9. Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–337.  https://doi.org/10.1038/nature11252 CrossRefGoogle Scholar
  10. Carr NJ, Mahajan H, Tan KL, Hawkins NJ, Ward RL (2009) Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma. J Clin Pathol 62:516–518.  https://doi.org/10.1136/jcp.2008.061960 CrossRefPubMedGoogle Scholar
  11. Day FL, Jorissen RN, Lipton L, Mouradov D, Sakthianandeswaren A, Christie M, Li S, Tsui C, Tie J, Desai J, Xu Z-Z, Molloy P, Whitehall V, Leggett BA, Jones IT, McLaughlin S, Ward RL, Hawkins NJ, Ruszkiewicz AR, Moore J, Busam D, Zhao Q, Strausberg RL, Gibbs P, Sieber OM (2013) PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer. Clin Cancer Res 19:3285–3296.  https://doi.org/10.1158/1078-0432.CCR-12-3614 CrossRefPubMedGoogle Scholar
  12. De Sousa E, Melo F, Wang X, Jansen M, Fessler E, Trinh A, de Rooij LPMH, de Jong JH, de Boer OJ, van Leersum R, Bijlsma MF, Rodermond H, van der Heijden M, van Noesel CJM, Tuynman JB, Dekker E, Markowetz F, Medema JP, Vermeulen L (2013) Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 19:614–618.  https://doi.org/10.1038/nm.3174 CrossRefGoogle Scholar
  13. Fearon ER (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol Mech Dis 6:479–507.  https://doi.org/10.1146/annurev-pathol-011110-130235 CrossRefGoogle Scholar
  14. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767.  https://doi.org/10.1016/0092-8674(90)90186-I CrossRefPubMedGoogle Scholar
  15. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386.  https://doi.org/10.1002/ijc.29210 CrossRefPubMedGoogle Scholar
  16. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E, Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:1350–1356.  https://doi.org/10.1038/nm.3967 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Isella C, Terrasi A, Bellomo SE, Petti C, Galatola G, Muratore A, Mellano A, Senetta R, Cassenti A, Sonetto C, Inghirami G, Trusolino L, Fekete Z, De Ridder M, Cassoni P, Storme G, Bertotti A, Medico E (2015) Stromal contribution to the colorectal cancer transcriptome. Nat Genet 47:312–319.  https://doi.org/10.1038/ng.3224 CrossRefPubMedGoogle Scholar
  18. Isella C, Brundu F, Bellomo SE, Galimi F, Zanella E, Porporato R, Petti C, Fiori A, Orzan F, Senetta R, Boccaccio C, Ficarra E, Marchionni L, Trusolino L, Medico E, Bertotti A (2017) Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer. Nat Commun 8:15107.  https://doi.org/10.1038/ncomms15107 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Jass JR (2007) Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 50:113–130.  https://doi.org/10.1111/j.1365-2559.2006.02549.x CrossRefPubMedGoogle Scholar
  20. Kim K-M, Lee EJ, Ha S, Kang SY, Jang K-T, Park CK, Kim JY, Kim YH, Chang DK, Odze RD (2011) Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea. Am J Surg Pathol 35:1274–1286.  https://doi.org/10.1097/PAS.0b013e318224cd2e CrossRefPubMedGoogle Scholar
  21. Marisa L, de Reyniès A, Duval A, Selves J, Gaub MP, Vescovo L, Etienne-Grimaldi M-C, Schiappa R, Guenot D, Ayadi M, Kirzin S, Chazal M, Fléjou J-F, Benchimol D, Berger A, Lagarde A, Pencreach E, Piard F, Elias D, Parc Y, Olschwang S, Milano G, Laurent-Puig P, Boige V (2013) Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 10:e1001453.  https://doi.org/10.1371/journal.pmed.1001453 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Matos P, Gonçalves V, Jordan P (2016) Targeting the serrated pathway of colorectal cancer with mutation in BRAF. Biochim Biophys Acta BBA – Rev Cancer 1866:51–63.  https://doi.org/10.1016/j.bbcan.2016.06.003 CrossRefGoogle Scholar
  23. Misale S, Di Nicolantonio F, Sartore-Bianchi A, Siena S, Bardelli A (2014) Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution. Cancer Discov 4:1269–1280.  https://doi.org/10.1158/2159-8290.CD-14-0462 CrossRefPubMedGoogle Scholar
  24. Obaid N, Bedard K, Huang W-Y (2017) Strategies for overcoming resistance in tumours harboring BRAF mutations. Int J Mol Sci 18:585.  https://doi.org/10.3390/ijms18030585 CrossRefPubMedCentralGoogle Scholar
  25. Perez Villamil B, Romera Lopez A, Hernandez Prieto S, Lopez Campos G, Calles A, Lopez Asenjo JA, Sanz Ortega J, Fernandez Perez C, Sastre J, Alfonso R, Caldes T, Martin Sanchez F, Diaz Rubio E (2012) Colon cancer molecular subtypes identified by expression profiling and associatedto stroma, mucinous type and different clinical behavior. BMC Cancer 12:260.  https://doi.org/10.1186/1471-2407-12-260 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Phipps AI, Limburg PJ, Baron JA, Burnett-Hartman AN, Weisenberger DJ, Laird PW, Sinicrope FA, Rosty C, Buchanan DD, Potter JD, Newcomb PA (2015) Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology 148:77–87.e2.  https://doi.org/10.1053/j.gastro.2014.09.038 CrossRefPubMedGoogle Scholar
  27. Roepman P, Schlicker A, Tabernero J, Majewski I, Tian S, Moreno V, Snel MH, Chresta CM, Rosenberg R, Nitsche U, Macarulla T, Capella G, Salazar R, Orphanides G, Wessels LF, Bernards R, Simon IM (2014) Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition: molecular subtypes in colorectal cancer. Int J Cancer 134:552–562.  https://doi.org/10.1002/ijc.28387 CrossRefPubMedGoogle Scholar
  28. Rosenberg DW, Yang S, Pleau DC, Greenspan EJ, Stevens RG, Rajan TV, Heinen CD, Levine J, Zhou Y, O’Brien MJ (2007) Mutations in BRAF and KRAS differentially distinguish serrated versus non-serrated hyperplastic aberrant crypt foci in humans. Cancer Res 67:3551–3554.  https://doi.org/10.1158/0008-5472.CAN-07-0343 CrossRefPubMedGoogle Scholar
  29. Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LCG, Lannon WA, Grotzinger C, Del Rio M, Lhermitte B, Olshen AB, Wiedenmann B, Cantley LC, Gray JW, Hanahan D (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19:619–625.  https://doi.org/10.1038/nm.3175 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Sandmeier D, Benhattar J, Martin P, Bouzourene H (2009) Serrated polyps of the large intestine: a molecular study comparing sessile serrated adenomas and hyperplastic polyps. Histopathology 55:206–213.  https://doi.org/10.1111/j.1365-2559.2009.03356.x CrossRefPubMedGoogle Scholar
  31. Schlicker A, Beran G, Chresta CM, McWalter G, Pritchard A, Weston S, Runswick S, Davenport S, Heathcote K, Castro DA, Orphanides G, French T, Wessels LF (2012) Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines. BMC Med Genet 5:66.  https://doi.org/10.1186/1755-8794-5-66 CrossRefGoogle Scholar
  32. Snover DC, Jass JR, Fenoglio-Preiser C, Batts KP (2005) Serrated polyps of the large intestine: a morphologic and molecular review of an evolving concept. Am J Clin Pathol 124:380–391.  https://doi.org/10.1309/V2EP-TPLJ-RB3F-GHJL CrossRefPubMedGoogle Scholar
  33. Velho S, Moutinho C, Cirnes L, Albuquerque C, Hamelin R, Schmitt F, Carneiro F, Oliveira C, Seruca R (2008) BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: primary or secondary genetic events in colorectal carcinogenesis? BMC Cancer 8:255.  https://doi.org/10.1186/1471-2407-8-255 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Whitehall VLJ, Rickman C, Bond CE, Ramsnes I, Greco SA, Umapathy A, McKeone D, Faleiro RJ, Buttenshaw RL, Worthley DL, Nayler S, Zhao ZZ, Montgomery GW, Mallitt K-A, Jass JR, Matsubara N, Notohara K, Ishii T, Leggett BA (2012) Oncogenic PIK3CA mutations in colorectal cancers and polyps. Int J Cancer 131:813–820.  https://doi.org/10.1002/ijc.26440 CrossRefPubMedGoogle Scholar
  35. Yang S, Farraye FA, Mack C, Posnik O, O’Brien MJ (2004) BRAF and KRAS mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status. Am J Surg Pathol 28:1452–1459.  https://doi.org/10.1097/01.pas.0000141404.56839.6a CrossRefPubMedGoogle Scholar
  36. Zhao L, Vogt PK (2010) Hot-spot mutations in p110alpha of phosphatidylinositol 3-kinase (pI3K): differential interactions with the regulatory subunit p85 and with RAS. Cell Cycle Georget Tex 9:596–600.  https://doi.org/10.4161/cc.9.3.10599 CrossRefGoogle Scholar
  37. Zhao B, Wang L, Qiu H, Zhang M, Sun L, Peng P, Yu Q, Yuan X (2017) Mechanisms of resistance to anti-EGFR therapy in colorectal cancer. Oncotarget 8:3980–4000.  https://doi.org/10.18632/oncotarget.14012 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Human GeneticsNational Health Institute ‘Dr. Ricardo Jorge’LisbonPortugal
  2. 2.BioISI – Biosystems & Integrative Sciences Institute, Faculty of SciencesUniversity of LisbonLisbonPortugal

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