Molecular Pathogenesis and Classification of Colorectal Carcinoma
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BASIC SCIENCE FOUNDATIONS IN COLORECTAL CANCER (S UMAR, SECTION EDITOR)
Molecular Pathogenesis and Classification of Colorectal Carcinoma Anup Kasi 1 & Shivani Handa 2 & Sajjad Bhatti 1 & Shahid Umar 3 & Ajay Bansal 4 & Weijing Sun 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Molecular pathways in colorectal carcinogenesis involve several complex genetic and epigenetic modulations that cause normal colonic mucosa to metamorphose into a benign polyp and subsequently into a malignant tumor. Our purpose is to recapitulate historical and recent genomic research in order to augment the understanding of colorectal cancer pathogenesis. Recent Findings In 2015, the molecular classification for colorectal cancers was unified into one system with four distinct groups, also called as consensus molecular subtypes. This led to an enhanced understanding of molecular and immune signatures which has implications on predicting the clinical behavior as well as response to different therapeutic agents. Summary In this review, we expound on the current literature as well as draw on our own experience to present the important molecular pathogenesis pathways, key genetic mutations, differences in pathogenesis of left versus right sided tumors as well as the molecular classification of colorectal cancers. Keywords Molecular pathogenesis . Colorectal carcinoma . Molecular subtypes
Introduction Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the USA, estimated to cause 53,200 deaths and 147,950 new cases in 2020 [1]. Sporadic colorectal cancer accounts for nearly 70% of the cases. Only 5% of the new colorectal cancer diagnoses are related to hereditary conditions such as the Lynch syndrome or familial adenomatous polyposis (FAP). Twenty to 30% of the cases have a familial
This article is part of the Topical Collection on Basic Science Foundations in Colorectal Cancer Drs. Kasi and Dr. Handa contributed equally to this manuscript and should be considered co-first authors * Anup Kasi [email protected] 1
Department of Medicine, Division of Medical Oncology, Kansas University Medical Center, Kansas City, KS, USA
2
Department of Internal Medicine, Icahn School of Medicine at Mount Sinai West & Morningside, New York, NY, USA
3
Department of Medicine, Division of Surgery, Kansas University Medical Center, Kansas City, KS, USA
4
Department of Medicine, Division of Gastroenterology, Kansas University Medical Center, Kansas City, KS, USA
disposition with no associated or known germline mutation [2]. Over the last few decades, our comprehension of the diverse genomic events in the pathogenesis of invasive colorectal cancer has improved significantly. Herein, we will describe the pathogenesis of colorectal cancer while touching upon the role of immune and stromal components in tumorigenesis as well as discuss the recently proposed molecular classification based on transcriptomics.
Molecular Pathogenesis Adenoma-Carcinoma Sequence An accruing body of evidence conti
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