Related Experiment Video

Updated: May 27, 2025

Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
15:17

Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing

Published on: September 25, 2011

13.9K

Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers

Hyun Gu Lee1, Yeseul Kim2, Mi-Ju Kim3

  • 1Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Cancer Research and Treatment
|February 20, 2025
PubMed
Abstract

Insights

Synchronous colorectal cancers (SCRCs) show significant molecular differences between tumors within the same patient. This intertumoral heterogeneity impacts targeted therapy, necessitating individual tumor molecular analysis for effective treatment selection.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Synchronous colorectal cancers (SCRCs) are diagnosed simultaneously and require distinct treatment strategies.
  • Understanding the molecular landscape of SCRCs is crucial for optimizing targeted therapy selection.
  • Limited data exists on the intertumoral heterogeneity of SCRCs.

Purpose of the Study:

  • To compare molecular characteristics and somatic mutations between synchronous colorectal cancers.
  • To evaluate intertumoral heterogeneity in SCRCs.
  • To assess the implications of molecular differences for targeted therapy.

Main Methods:

  • Retrospective analysis of 98 patients with surgically resected SCRCs (2012-2014).
  • Analysis of microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs) for all lesions.
  • Whole-exome sequencing (WES) of 18 cancers from 9 patients with at least one MSI-high (MSI-H) tumor.

Main Results:

  • Discordant MSI status was observed in 5 out of 12 patients with at least one MSI-H tumor.
  • Mucinous adenocarcinoma frequency and TIL density were higher in patients with MSI-H tumors.
  • WES revealed low variant sharing (0.09-0.36%) between synchronous cancers within patients, indicating significant intertumoral heterogeneity.
  • Concordance rates for common mutations (BRAF, KRAS, NRAS, PIK3CA) were moderate, ranging from 55.6% to 66.7%.

Conclusions:

  • SCRCs exhibit substantial intertumoral heterogeneity in molecular profiles and somatic mutations.
  • Discordance in MSI status and somatic variants can occur between synchronous tumors.
  • Molecular analysis of all synchronous tumors is recommended to guide personalized targeted therapy selection.
Keywords:
Colorectal neoplasmsExome sequencingMicrosatellite instabilitySynchronousTumor-infiltrating lymphocytes

More Related Videos

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts10:33

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts

Published on: April 29, 2014

11.0K
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis09:45

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Published on: March 31, 2015

11.1K

Related Concept Videos

Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.4K