Related Experiment Video
Updated: Jun 7, 2025
Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Switch/Sucrose Nonfermentable-Deficient Tumors-Morphology, Immunophenotype, Genetics, Epigenetics, Nosology, and
1Department of Pathology, Caritas Medical Center, Kowloon, Hong Kong.
Abstract:
About 20% of human cancers harbor mutations of genes encoding switch/sucrose nonfermentable (SWI/SNF) complex subunits. Deficiency of subunits of the complex is present in 10% of non-small-cell lung cancers (NSCLC; SMARCA4/SMARCA2 deficient), 100% thoracic SMARCA4/A2-deficient undifferentiated tumors (TSADUDT; SMARCA4/A2 deficient), malignant rhabdoid tumor, and atypical/teratoid tumor (SMARCB1-deficient), >90% of small cell carcinoma of the ovary, hypercalcemic type (SMARCA4/SMARCA2 deficient), frequently in undifferentiated/dedifferentiated endometrial carcinoma (SMARCA4, SMARCA2, SMARCB1, and ARID1A/B deficient), 100% SMARCA4 deficient undifferentiated uterine sarcoma (SMARCA4 deficient); and in various other tumors from multifarious anatomical sites. Silencing of SWI/SNF gene expression may be genomically or epigenetically driven, causing loss of tumor suppression function or facilitating other oncogenic events. The SWI/SNF-deficient tumors share the phenotype of poor or no differentiation, often with a variable component of rhabdoid tumor cells. They present at advanced stages with poor prognosis. Rhabdoid tumor cell phenotype is a useful feature to prompt investigation for this group of tumors. In the thoracic space, the overlap in morphology, immunophenotype, genetics, and epigenetics of SMARCA4/A2-deficient NSCLC and TSADUDT appears more significant. This raises a possible nosologic relationship between TSADUDT and SMARCA4/A2-deficient NSCLC. Increased understanding of the genetics, epigenetics, and mechanisms of oncogenesis in these poor prognostic tumors, which are often resistant to conventional treatment, opens a new horizon of therapy for the tumors.
Insights
Mutations in SWI/SNF genes occur in 20% of human cancers, leading to undifferentiated tumors with poor prognosis. Understanding these SWI/SNF-deficient cancers offers new therapeutic avenues.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Approximately 20% of human cancers involve mutations in genes encoding switch/sucrose nonfermentable (SWI/SNF) complex subunits.
- SWI/SNF complex gene deficiencies are implicated in various cancers, including non-small-cell lung cancer (NSCLC), thoracic SMARCA4/A2-deficient undifferentiated tumors (TSADUDT), malignant rhabdoid tumors, and endometrial carcinomas.
Purpose of the Study:
- To investigate the role of SWI/SNF complex subunit deficiencies in tumorigenesis and cancer progression.
- To explore the potential nosologic relationship between TSADUDT and SMARCA4/A2-deficient NSCLC.
- To identify new therapeutic strategies for SWI/SNF-deficient tumors.
Main Methods:
- Analysis of genetic and epigenetic alterations in SWI/SNF-deficient tumors.
- Comparative study of morphology, immunophenotype, genetics, and epigenetics between TSADUDT and SMARCA4/A2-deficient NSCLC.
- Review of existing literature on SWI/SNF complex function in cancer.
Main Results:
- SWI/SNF gene silencing, whether genomic or epigenetic, can lead to loss of tumor suppressor function or promote oncogenic events.
- SWI/SNF-deficient tumors often exhibit poor differentiation, rhabdoid morphology, advanced stage at presentation, and poor prognosis.
- Significant overlap in molecular and morphological features between SMARCA4/A2-deficient NSCLC and TSADUDT suggests a potential nosologic link.
Conclusions:
- SWI/SNF-deficient tumors represent a distinct group with shared phenotypic and prognostic characteristics.
- The rhabdoid tumor cell phenotype is a key indicator for investigating this tumor group.
- Further understanding of SWI/SNF-deficient oncogenesis may pave the way for novel therapeutic interventions.
More Related Videos
Related Concept Videos
01:27Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:27Tumor Immunotherapy