Updates on the Molecular Genetics of Colorectal Cancer

Katherine Wong,Guofeng Xie

doi:10.21767/2471-9943.100032

Abstract

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although definitive therapies for advanced disease are still lacking, rapid progress has been made in the last decade in understanding the molecular mechanisms underlying CRC tumorigenesis and progression. In this review, we summarize the most recent findings in the molecular genetics of CRC with a focus on gene mutations and epigenetic changes that were identified in CRC patients.

Highlights

Colorectal cancer (CRC) is one of the most prevalent malignancies in the USA
Chromosomal instability (CIN) and microsatellite instability (MSI) are two molecular pathways that have been described in the progression to colorectal cancer [7,8]. 65-70% of sporadic cancers arise from the CIN pathway, which is defined by insertion, deletion, or rearrangement of entire chromosomal regions [7]
THO complex 1 (Thoc1) is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC

Summary

Introduction

Colorectal cancer (CRC) is one of the most prevalent malignancies in the USA. With an estimated incidence of 134,490 new cases and 49,190 deaths in 2016, it is the third most common cause of cancer as well as cancer mortality in both men and women, with a five-year survival rate of less than 15% [1,2]. MSI is characterized by a genetic or epigenetic defect in DNA repair, leading to loss of function of the MMR protein and mismatch mutations [9,10]. It accounts for 15% of CRC cases (12% sporadic, 3% due to Lynch syndrome) and it is a part of the serrated pathway [11]. Results revealed that a homozygous c.672_673delGGinsC mutation in MCM9 (chr6:119243200) was present in both sisters, while other healthy family members were heterozygous This mutation caused a frame shift leading to premature truncation associated with polyposis and early-onset CRC [14].

Type of Study

Disruptive mutation Mutation causes polymerase proofreadingassociated polyposis

Gastric mucin gene linked to the serrated pathway in CRC formation

Single nucleotide polymorphisms

Future Directions