Related Experiment Video

Updated: Mar 8, 2026

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
09:01

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Published on: July 3, 2025

1.1K

Pancancer modelling predicts the context-specific impact of somatic mutations on transcriptional programs

Hatice U Osmanbeyoglu1, Eneda Toska2, Carmen Chan2

  • 1Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box No. 460, New York, New York 10065, USA.

Nature Communications
|February 1, 2017
PubMed

Insights

Piecemeal cancer therapies targeting specific gene mutations may not work across all cancer types. This study reveals how the same mutation affects gene activity differently in various cancers, impacting targeted treatment strategies.

Area of Science:

  • Genomics
  • Cancer Biology
  • Computational Biology

Background:

  • Pancancer studies identify frequently altered genes, suggesting broad applicability of pathway-targeted therapies.
  • However, the impact of 'actionable mutations' varies context-specifically across different tumor types and genetic backgrounds.

Purpose of the Study:

  • To computationally integrate proteomic and mRNA sequencing data across 12 TCGA datasets.
  • To interpret the context-specific impact of somatic alterations on functional signatures, including protein and transcription factor activities.

Main Methods:

  • Applied a computational strategy to integrate parallel (phospho)proteomic and mRNA sequencing data.
  • Analyzed 12 The Cancer Genome Atlas (TCGA) tumor datasets.
  • Interpreted somatic alteration impacts using functional signatures like (phospho)protein and transcription factor (TF) activities.

Main Results:

  • Predicted distinct dysregulated transcriptional regulators downstream of somatic alterations in different cancers.
  • Validated context-specific differential TF activity associated with mutant PIK3CA in isogenic cancer cell line models.

Conclusions:

  • Somatic alterations have context-specific impacts on gene regulatory programs and signaling networks.
  • Findings have implications for the pancancer use of targeted drugs and combination therapy design.

More Related Videos

Author Spotlight: Impact of Intergenic Interactions on Disease-Identifying Dark Biomarkers03:37

Author Spotlight: Impact of Intergenic Interactions on Disease-Identifying Dark Biomarkers

Published on: March 1, 2024

1.4K
Syngeneic Mouse Orthotopic Allografts to Model Pancreatic Cancer06:20

Syngeneic Mouse Orthotopic Allografts to Model Pancreatic Cancer

Published on: October 4, 2022

4.1K

Related Concept Videos

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
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...
11.7K
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
6.6K
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...
10.0K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.2K