Molecular Characterization of Colorectal Cancers

Sally Lewis; Dale Telgenhoff; Brooke Dubansky

doi:10.29074/ascls.2022003208

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Figure 1.
NextGen Sequencing. Next-generation sequencing (NGS) is a powerful platform that enables the sequencing of millions of DNA molecules from multiple patients simultaneously.

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Table 1.

Selected hereditary colorectal cancer

Selected Hereditary Colorectal Cancer Syndromes
Syndrome	Gene(s)	Mode of Inheritance
FAP	APC	Dominant
Hereditary nonpolyposis colorectal cancer	MLH1, MSH2, MSH6, PMS2, TACSTD1	Dominant
MYH-polyposis	MUTYH	Recessive

Discovery of germline mutations in these syndromes has been critical to understanding the molecular mechanisms of CRC. (adapted from Ma et al. (2018) Pathology and genetics of hereditary colorectal cancer)¹⁶

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Table 2.

Consensus molecular subtypes of CRC

Consensus Molecular Subtypes of CRC
Subtype	Features	Percent of Total
CMS1 (MSI immune)	Hypermutated Microsatellite instability Strong immune activation	14%
CMS2 (canonical)	Epithelial Chromosomally unstable Marker Wnt and MYC activation	37%
CMS1 (metabolic)	Metabolic Evident metabolic dysregulation	13%
CMS1 (mesenchymal)	Prominent TGF-β activation Stromal invasion Angiogenesis	23%

An international consortium led by Guinney at Fred Hutchinson Cancer Research Center and other institutions has grouped molecular subtypes of CRC into a classification as the future basis for subtype-based targeted interventions.³⁵