Study Revealed Genetic Secrets of Colorectal Cancer

Researchers recently used whole-genome sequencing (WGS) of 2,023 samples to provide a thorough genomic characterisation of colorectal carcinoma (CRC), a type of cancer that begins in the colon or rectum. They were able to identify novel driver genes, molecular subgroups, and potential clinical implications. The study was published in Nature.

Background

colorectal cancer (CRC) is the third most common cancer worldwide. Previous efforts to sequence CRCs were narrowly focused, concentrating on a small number of cases and mainly utilising whole-exome or gene panel sequencing, which left the full spectrum of genomic alterations and clinical associations unclear. More investigation is required to determine the functional significance of recently discovered driver mutations and to create targeted therapies for different CRC subgroups.

About the study
A comprehensive protocol was followed in order to acquire the study’s sample, starting with ethics approval from the East of England-Cambridge South research ethics committee of the Health Research Authority (HRA). Thirteen Genomic Medicine Centres (GMCs) were developed by the National Health Services (NHS) and the 100,000 Genomes Project (100kGP) as a high-throughput tumour sequencing project for cancer patients. The program made sample collecting easier.

All participants gave written informed consent, and patients scheduled for CRC resections were selected by specialist nurses and other staff members. Blood was drawn, tumour samples were assessed in histopathology cut-ups, and related clinicopathological information was obtained from medical records.

Following an evaluation of frozen tumour subsamples for purity and further histological features, blood and tumour samples that passed quality control were forwarded to local genetics labs for the extraction of deoxyribonucleic acid (DNA). After the extracted DNA was moved to the 100kGP Central National Biorepository, Illumina carried out Whole Genome Sequencing (WGS) on matched tumor-constitutional DNA.

The Binary Alignment/Map (BAM) files that had been processed were subsequently sent to Genomics England for quality assurance, further processing, and data storage. The clinicopathological and sequencing data were then moved to the Colorectal Cancer Domain (GECIP) for additional quality control and data analysis, guaranteeing the completeness and accuracy of the genomic data used in this investigation.

In conclusion
In summary, this work offers a thorough examination of the genomic landscape of colorectal cancer (CRC), revealing a multitude of new driver mutations, SVs, and CNAs in addition to emphasising the unique molecular traits of the MSI, MSS, and POL subtypes. The results provide important new understandings of the intricate biology of colorectal cancer and possible directions for tailored treatment.

For more information: The genomic landscape of 2,023 colorectal cancers, Nature, https://doi.org/10.1038/s41586-024-07747-9