Related Experiment Video

Updated: Jun 4, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer

Cecily P Vaughn1, Scott D Zobell, Larissa V Furtado

  • 1ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA.

Genes, Chromosomes & Cancer
|February 10, 2011
PubMed

Insights

Mutations in KRAS codons 12/13 are standard for colorectal cancer patients. Testing additional RAS pathway genes like BRAF and NRAS in KRAS wildtype tumors identified resistance mutations in 27.3% of patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Mutational analysis of KRAS codons 12 and 13 is standard for metastatic colorectal cancer (mCRC) patients, predicting response to anti-EGFR therapies.
  • A subset of patients with wildtype KRAS codons 12 and 13 still exhibit resistance to anti-EGFR therapy, suggesting other mutations may be involved.

Purpose of the Study:

  • To determine the frequency of mutations in other RAS pathway genes (KRAS codons 61 and 146, BRAF codon 600, NRAS codons 12, 13, and 61) in mCRC patients wildtype for KRAS codons 12 and 13.
  • To assess the potential role of these additional mutations in resistance to anti-EGFR therapies.

Main Methods:

  • Evaluated 2121 colorectal tumors for mutations in KRAS codons 12 and 13.
  • Utilized targeted pyrosequencing to analyze mutations in KRAS codons 61 and 146, BRAF codon 600, and NRAS codons 12, 13, and 61 in 513 samples wildtype for KRAS codons 12 and 13.

Main Results:

  • Mutations in KRAS codons 12 or 13 were found in 42.4% (900/2121) of samples.
  • In the subset of 513 wildtype samples, 140 (27.3%) harbored mutations in other RAS pathway genes: BRAF (78), KRAS codon 61 (19), KRAS codon 146 (17), and NRAS (26).

Conclusions:

  • A significant proportion (27.3%) of KRAS wildtype mCRC tumors harbor mutations in other RAS pathway genes.
  • Mutational testing of these additional codons may help identify patients resistant to anti-EGFR therapies, warranting further investigation into their therapeutic implications.

More Related Videos

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells06:44

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells10:13

A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

Published on: July 3, 2013

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...