Related Experiment Video

Updated: Mar 6, 2026

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
07:59

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

Published on: September 8, 2023

1.8K

Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor

Alexa B Schrock1, Shuyu D Li2, Garrett M Frampton1

  • 1Foundation Medicine, Inc., Cambridge, Massachusetts.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|March 20, 2017
PubMed
Abstract

Insights

Pulmonary sarcomatoid carcinoma (PSC) is a rare NSCLC with poor prognosis. Comprehensive genomic profiling reveals actionable targets and high tumor mutational burden, offering new treatment avenues.

Area of Science:

  • Oncology
  • Genomics
  • Pulmonary Medicine

Background:

  • Pulmonary sarcomatoid carcinoma (PSC) is an aggressive non-small cell lung cancer (NSCLC) subtype.
  • PSC is associated with poor prognosis and resistance to conventional chemotherapy.
  • Limited molecular characterization has hindered the development of targeted therapies for PSC.

Purpose of the Study:

  • To comprehensively characterize the genomic landscape of PSC.
  • To identify potentially targetable genomic alterations (GAs) and assess tumor mutational burden (TMB) in PSC.
  • To explore the utility of comprehensive genomic profiling (CGP) in guiding treatment decisions for PSC patients.

Main Methods:

  • Hybrid capture-based CGP was performed on 15,867 NSCLC cases, including 125 PSCs.
  • Tumor mutational burden (TMB) was calculated from sequenced DNA.
  • Genomic alterations were analyzed in key NSCLC-related genes.

Main Results:

  • TP53 GAs were found in 74% of PSC cases.
  • KRAS, MET, EGFR, BRAF, HER2, and RET alterations were identified in 62% of PSCs.
  • MET exon 14 alterations were significantly enriched in PSC (12%) compared to non-PSC NSCLC (3%).
  • A higher fraction of PSC cases exhibited high TMB (>20 mutations/Mb) compared to non-PSC NSCLC (20% vs. 14%).
  • Among nine patients treated with targeted or immunotherapies, six showed clinical benefit (partial response or stable disease).

Conclusions:

  • Most PSC cases harbor potentially targetable GAs or intermediate/high TMB.
  • CGP can identify actionable targets in PSC, a historically challenging disease.
  • Genomic profiling may offer crucial treatment options for PSC patients.
Keywords:
BRAFGenomic profilingImmunotherapyLung sarcomatoidMET exon 14Tumor mutational burden

More Related Videos

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

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

Published on: September 20, 2016

25.2K
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

9.9K

Related Concept Videos

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...
5.3K
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...
7.6K
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...
15.2K