Related Experiment Video

Updated: Oct 12, 2025

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

9.7K

The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer

Hiroki Izumi1, Shingo Matsumoto1, Jie Liu2

  • 1Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Nature
|November 25, 2021
PubMed

Insights

Researchers discovered a new CLIP1-LTK fusion in non-small cell lung cancer (NSCLC). This fusion is targetable with lorlatinib, offering a potential new treatment for NSCLC patients lacking other known drivers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Non-small cell lung cancer (NSCLC) treatments are improving with targeted therapies.
  • However, a significant portion of lung adenocarcinoma cases lack identified oncogenic drivers.
  • This highlights the need for novel therapeutic targets in NSCLC.

Purpose of the Study:

  • To identify novel oncogenic drivers in NSCLC.
  • To investigate the therapeutic potential of targeting identified fusions.
  • To evaluate the efficacy of lorlatinib against novel NSCLC targets.

Main Methods:

  • Whole-transcriptome sequencing was employed using a multi-institutional genome screening platform.
  • CLIP1-LTK fusion was identified and characterized.
  • Functional assays were performed in Ba/F3 cells, and a patient case study was analyzed.

Main Results:

  • A novel CLIP1-LTK fusion transcript was identified in 0.4% of NSCLCs, mutually exclusive with known drivers.
  • The CLIP1-LTK fusion protein exhibits constitutive kinase activity and transformation potential.
  • Lorlatinib effectively inhibited CLIP1-LTK activity, suppressed proliferation, and induced apoptosis in vitro.
  • A patient with NSCLC harboring the CLIP1-LTK fusion responded well to lorlatinib.

Conclusions:

  • The CLIP1-LTK fusion represents a newly identified oncogenic driver in NSCLC.
  • This fusion is the first described LTK alteration with oncogenic activity in cancer.
  • CLIP1-LTK fusion is a potential therapeutic target for NSCLC, treatable with lorlatinib.

More Related Videos

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

18.1K
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

2.9K

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.0K
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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.9K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.5K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.2K