Related Experiment Video

Updated: Dec 23, 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

24.8K

IDH1 and IDH2 mutations in lung adenocarcinomas: Evidences of subclonal evolution

Erika F Rodriguez1, Federico De Marchi1, Parvez M Lokhandwala1

  • 1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Cancer Medicine
|April 26, 2020
PubMed
Abstract

Insights

Isocitrate dehydrogenase (IDH1/2) mutations are rare in non-small cell lung cancers (NSCLCs), occurring in high-grade adenocarcinomas. These mutations may act as branching drivers, contributing to subclonal evolution in lung cancer development.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Selective inhibitors targeting isocitrate dehydrogenase 1 and 2 (IDH1/2) are approved for acute myeloid leukemia.
  • Clinical trials are ongoing for solid tumors with IDH1/2 mutations.
  • Reports on IDH1/2-mutated non-small cell lung cancers (NSCLCs) are limited.

Purpose of the Study:

  • To evaluate the frequency and characteristics of IDH1/2 mutations in a large cohort of NSCLC specimens.
  • To investigate the clinicopathological associations and potential role of IDH1/2 mutations in NSCLC pathogenesis.

Main Methods:

  • Next-generation sequencing was used to analyze IDH1/2 mutations in 1,924 NSCLC specimens, predominantly adenocarcinomas.
  • Retrospective quality assessment was performed to identify potential artifacts.

Main Results:

  • IDH1/2 mutations were detected in 0.5% of NSCLC adenocarcinomas, all exhibiting high-grade features.
  • IDH1/2 mutations were associated with older age, smoking history, and coexisting KRAS mutations.
  • Evidence suggests IDH1/2 mutations may function as branching drivers, promoting subclonal evolution in lung adenocarcinomas.

Conclusions:

  • IDH1/2 mutations are uncommon in NSCLCs and are found in high-grade adenocarcinomas.
  • These mutations might play a role as branching drivers in the subclonal evolution of NSCLC.
  • Further accumulation of IDH1/2-mutated NSCLC cases is necessary to fully understand their characteristics and therapeutic implications.
Keywords:
IDH1IDH2cytosine deaminationlung cancersparallel evolution

More Related Videos

Comparative Lesions Analysis Through a Targeted Sequencing Approach08:16

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

7.1K
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas06:27

A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas

Published on: May 9, 2025

971

Related Concept Videos

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...
9.3K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.8K
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...
14.4K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.0K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.1K