Related Experiment Video

Updated: Oct 20, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

24.6K

Characterization of KRAS Mutation Subtypes in Non-small Cell Lung Cancer

Julia Judd1, Nagla Abdel Karim2, Hina Khan3

  • 1Department of Hematology-Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.

Molecular Cancer Therapeutics
|September 14, 2021
PubMed

Insights

KRAS mutations are common in non-small cell lung cancer (NSCLC). Different KRAS subtypes, like G12C, show distinct genomic profiles and PD-L1 expression, impacting treatment strategies.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • KRAS is a frequently mutated oncogene in non-small cell lung cancer (NSCLC).
  • Targeted KRAS inhibitors are emerging, increasing interest in understanding KRAS mutation subtypes.
  • Different KRAS mutations may influence prognosis and treatment response.

Purpose of the Study:

  • To characterize the genomic landscape of advanced KRAS-mutated NSCLC.
  • To identify co-occurring alterations, tumor mutational burden (TMB), and PD-L1 expression across KRAS mutation subtypes.
  • To guide future therapeutic development for KRAS-mutated NSCLC.

Main Methods:

  • DNA next-generation sequencing of 592 genes was performed on 17,095 NSCLC specimens.
  • Specimens were classified based on KRAS mutation presence and subtype.
  • Analysis included co-occurring genomic alterations, TMB, and PD-L1 expression (22C3, TPS).

Main Results:

  • KRAS mutations were found in 27.5% of NSCLC cases, with G12C (40%), G12V (19%), and G12D (15%) being most common.
  • KRAS G12C was associated with higher PD-L1 positivity (65.5%) and high PD-L1 expression (41.3%).
  • STK11 mutations were more frequent in KRAS-mutant NSCLC, particularly G13 (36.2%), while TP53 mutations were more common in KRAS wild-type NSCLC (73.6%).

Conclusions:

  • KRAS mutation subtypes exhibit distinct co-occurring mutations and genomic landscapes.
  • These genomic differences may have clinical relevance for specific therapeutic interventions.
  • Further investigation is warranted to explore the clinical utility of these findings.

More Related Videos

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer07:59

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

1.3K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.2K

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...
6.6K
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:
4.4K
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...
4.7K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
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...
13.3K