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Oncogenetics of Colorectal Cancer (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: 1 July 2026 | Viewed by 1069

Special Issue Editors


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Guest Editor
1. Institute for Population and Precision Health (IPPH), Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA
2. Department of Public Health Sciences, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA
Interests: colorectal carcinoma; microsatellite instability; cytogenetics; molecular genomics; GWAS; copy number change; telomere; methylation; liquid biopsy
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL 60637, USA
Interests: colonoscopy; colon cancer; factors for growth signaling; miRNA; Vitamin D
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of "Oncogenetics of Colorectal Cancer".

Colorectal carcinoma (CRC) is one of the most common cancers worldwide. It represents a heterogeneous group of disorders from a molecular genomic point of view. Sporadic CRC is the most common form and is associated with somatic mutations, DNA methylation, genomic instability in the form of copy number changes, and microsatellite instability. Inflammatory pathways and host immune response have been associated not only with pathogenesis but also targeted therapeutic options. Many of the changes occurring are also reflected in liquid biopsy samples. Full use of known and yet-to-be-known molecular changes in tumor tissue and/or liquid biopsy for predictive, diagnostic, therapeutic, and prognostic purposes could improve personalized therapy.

This Special Issue focuses on original research papers and review articles on different molecular genomic and epigenetic changes in CRC tissue and liquid biopsy, their association with the pathogenesis of CRC, and therapeutic applications and outcomes.

Dr. Muhammad Kibriya
Dr. Marc Bissonnette
Guest Editors

Manuscript Submission Information

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Keywords

  • colorectal carcinoma
  • somatic mutation
  • microsatellite instability
  • methylation
  • copy number change
  • tumor-infiltrating leukocyte
  • immune checkpoint inhibitor
  • drug resistance
  • cell-free DNA

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Published Papers (1 paper)

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Research

14 pages, 952 KB  
Article
Prognostic Impact of Blood Tumor Mutational Burden in pMMR/MSS Metastatic Colorectal Cancer Assessed by FoundationOne® Liquid CDx
by Benoist Chibaudel, Elisabeth Carola, Hamid Mekranter, Perrine Goyer, Arnaud Saget, Olivier Oberlin, Hélène Marijon, Hubert Richa, Ida Iurisci, Honorine Gervais, Nathalie Perez-Staub, Linda Dainese, Pascal Pujol, Hanah Lamallem, Clémentine Besnard, Sofya Latrache, Alain Toledano and Aimery de Gramont
Cancers 2026, 18(3), 515; https://doi.org/10.3390/cancers18030515 - 4 Feb 2026
Viewed by 742
Abstract
Background/Objectives: The prognostic significance of blood tumor mutational burden (bTMB) in metastatic colorectal cancer (mCRC) remains poorly defined. While tissue-based TMB has been associated with favorable outcomes in selected colorectal cancer subgroups, the clinical meaning of bTMB in real-world practice is unclear. This [...] Read more.
Background/Objectives: The prognostic significance of blood tumor mutational burden (bTMB) in metastatic colorectal cancer (mCRC) remains poorly defined. While tissue-based TMB has been associated with favorable outcomes in selected colorectal cancer subgroups, the clinical meaning of bTMB in real-world practice is unclear. This study evaluated the prognostic impact of bTMB measured through liquid biopsy in an unselected cohort of patients with mCRC. Methods: This monocentric, real-world study included 255 adult patients with pMMR/MSS mCRC who underwent routine comprehensive genomic profiling using the FoundationOne® Liquid CDx assay. bTMB was quantified in mutations per megabase (mut/Mb), and patients were classified into bTMB-low and bTMB-high groups using the cohort median. The primary endpoint was overall survival (OS). Subgroup analyses, including stratification by RAS/BRAF mutation status, were descriptive. Results: The median bTMB was 5 mut/Mb. Patients in the bTMB-high group had an increased risk of death compared with those in the bTMB-low group (hazard ratio (HR) 1.88). The adverse prognostic effect for OS of high bTMB was more pronounced in patients with RAS mutant tumors (HR 2.32) than with RAS/BRAF wild-type tumors (HR 1.81), while no prognostic impact was observed in BRAFV600E mutant tumors (HR 0.90). bTMB was strongly correlated with ctDNA fraction (p < 0.0001). Conclusions: In routine clinical practice, elevated bTMB is associated with poor prognosis in pMMR/MSS mCRC, particularly in RAS mutant tumors. These results contrast with prior tissue-based studies and indicate that bTMB may reflect tumor burden and aggressive disease biology rather than tumor immunogenicity. Prospective studies integrating bTMB with ctDNA fraction, tumor burden metrics, and longitudinal molecular dynamics are warranted to refine its clinical utility. Full article
(This article belongs to the Special Issue Oncogenetics of Colorectal Cancer (2nd Edition))
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