Related Experiment Video

Updated: Aug 15, 2026

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies
13:24

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Published on: April 11, 2016

The pan-tumor landscape, allelic status, and genomic complexity of SMARCA4 alterations

Matteo Repetto1, Michael V Gormally2, Jason Chang1

  • 1Memorial Sloan Kettering Cancer Center New York, NY United States.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 14, 2026
PubMed
Abstract

Insights

Distinct SMARCA4 alteration classes and allelic status define unique tumor subsets. These findings aid patient selection for novel BRM-targeted therapies, improving treatment outcomes.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • SMARCA4 alterations are implicated in various cancers, but their clinical relevance is not fully understood.
  • Understanding different SMARCA4 mutation classes is crucial for targeted therapy development.

Purpose of the Study:

  • To conduct a pan-cancer analysis of SMARCA4 alteration classes.
  • To associate these classes with allelic status, genomic context, and therapeutic outcomes.

Main Methods:

  • Analysis of 68,920 tumor-normal paired samples using MSK-IMPACT sequencing.
  • Curation and classification of SMARCA4 alterations using OncoKB and literature.
  • Evaluation of genomic complexity and clinical outcomes in treated cohorts.

Main Results:

  • SMARCA4 alterations are frequent in thymic epithelial tumors, NSCLC, bladder, and cervical cancers.
  • Distinct genomic patterns and co-occurring alterations observed based on SMARCA4 alteration class and allelic state.
  • Patients with monoallelic class 2 SMARCA4 alterations and preserved BRG1 expression showed clinical benefit in a BRM degrader trial.

Conclusions:

  • SMARCA4 alteration class and allelic status identify distinct tumor subsets with unique biological and clinical features.
  • Incorporating allelic status and functional mutation class is recommended for patient selection in emerging BRM-targeted therapies.

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

Related Concept Videos

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...
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...
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...
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...
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...