Related Experiment Video

Updated: Apr 27, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

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

Published on: June 27, 2020

3.9K

CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression

Steven Christopher Smith1, Darya Buehler2, Eun-Young Karen Choi3

  • 11] Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA [2] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|June 21, 2014
PubMed

Insights

CIC-DUX sarcomas, a novel aggressive cancer subgroup, show frequent MYC amplification and expression. This finding suggests MYC may be a therapeutic target in these undifferentiated round cell sarcomas.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Cancer Genomics

Background:

  • CIC-DUX sarcomas are a recently identified, aggressive subgroup of undifferentiated round cell sarcomas.
  • These tumors are characterized by specific molecular fusions involving the CIC gene and either DUX4 or DUX4L.
  • Morphological features include high-grade nuclear characteristics, clear cell foci, myxoid change, and necrosis.

Purpose of the Study:

  • To investigate the molecular alterations, particularly MYC pathway involvement, in a cohort of CIC-DUX sarcomas.
  • To assess the expression of ETS-family transcription factors in these tumors.
  • To evaluate potential therapeutic targets within CIC-DUX sarcomas.

Main Methods:

  • Analysis of a cohort of 10 CIC-DUX sarcoma cases, including 6 new cases and 2 with metastases.
  • Assays for trisomy 8, MYC (c-Myc) amplification and expression, and MYC downstream targets (p21, MTDH).
  • Immunohistochemical analysis for ERG and FLI1 expression.

Main Results:

  • Trisomy 8 was detected in 5/7 assessable cases.
  • MYC locus amplification was found in 6/7 cases, with universal MYC protein expression (10/10).
  • ERG (9/10) and FLI1 (8/8) positivity was prevalent, while p21 showed differential expression compared to Ewing sarcomas.

Conclusions:

  • MYC amplification and expression are highly prevalent in CIC-DUX sarcomas, indicating a potential therapeutic vulnerability.
  • The frequent expression of ERG and FLI1 necessitates caution in their use as sole diagnostic markers.
  • These findings highlight MYC as a promising therapeutic target for aggressive CIC-DUX sarcomas.

More Related Videos

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

8.4K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

6.5K

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...
4.0K
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...
4.8K
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...
8.9K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.0K
Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.0K