Molecular Classification

**3**

**Chapter 1**

Cancer

**Abstract**

will be briefly explored.

**1. Introduction**

gene expression profiles, colorectal cancer

Advances in Molecular

*Avani Athauda and Ian Chau*

Subclassification of Colorectal

This chapter will highlight the advances made in our understanding of the molecular landscape of colorectal cancer (CRC) via the development of molecular subclassification systems and their potential predictive and prognostic utility. Firstly, the comprehensive integrative analysis of 224 colorectal cancer samples performed by The Cancer Genome Atlas (TCGA) Research Network will be described highlighting the potential therapeutic targets identified. The development of molecular subclassification systems primarily via gene expression profile analysis by independent groups will also be described, and their potential clinical and prognostic associations will also be discussed. The chapter will then go on to describe the four consensus molecular subtypes of colorectal cancer which were proposed by an international consortium who applied unsupervised clustering techniques to the independent classification systems previously described. The clinical and prognostic associations of these four subtypes have been explored, and these findings will be discussed. Finally, the utility of molecular subclassification in colorectal cancer

**Keywords:** molecular subclassification, consensus molecular subtypes,

Colorectal cancer (CRC) was one of the earliest molecularly characterised solid

tumours. Vogelstein et al. initially described the stepwise manner of adenoma formation to carcinoma via the accumulation of genetic and epigenetic events in the late 1980s [1]. This model provided insight into how driver alterations in the main oncogenes (KRAS, NRAS, BRAF and PI3K) and tumour suppressor genes (APC, TP53 and PTEN) were implicated in the biology of CRC [2]. The accumulation of these genetic mutations leads to carcinogenesis through deregulation of key pathways involved in cell proliferation, differentiation and apoptosis. It is now known that abnormalities of the Wnt signalling pathway are almost ubiquitous in sporadic

Further to this, genetic and epigenetic exploration of CRC subsequently identified significant molecular heterogeneity in this disease. This was clinically evident by the differing responses to systemic therapy and varying clinical course of patients with the same stage of tumour. Biomarker discovery in CRC has arisen

CRC and usually arise from mutations of the APC gene [3].
