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Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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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.
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Tumor Progression02:07

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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.
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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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Related Experiment Video

Updated: May 22, 2026

gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair
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Published on: October 6, 2014

Evolutionary pathways in BRCA1-associated breast tumors.

Filipe C Martins1, Subhajyoti De, Vanessa Almendro

  • 1Departments of Medical Oncology, Brigham and Women's Hospital, USA.

Cancer Discovery
|May 26, 2012
PubMed
Summary

BRCA1 breast tumors show PTEN loss as a common early event, particularly in basal-like subtypes. TP53 mutations often initiate luminal tumors, impacting therapeutic strategies for BRCA1 carriers.

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • BRCA1-associated breast tumors are characterized by BRCA1 loss and frequent mutations in PTEN and TP53.
  • Understanding the sequence of these genetic events is crucial for targeted therapies.

Purpose of the Study:

  • To analyze BRCA1, PTEN, and p53 alterations at the single-cell level in BRCA1-associated breast tumors.
  • To computationally predict the temporal order of somatic events.
  • To investigate intratumor heterogeneity and its implications in BRCA1 mutation carriers.

Main Methods:

  • Single-cell analysis of BRCA1, PTEN, and p53 in 55 BRCA1-associated breast tumors.
  • Development of computational methods to infer the order of somatic alterations based on cellular frequency.
  • Assessment of cell proliferation and centrosome amplification in normal breast epithelium of carriers.

Main Results:

  • Loss of PTEN is the most frequent initial event, associated with the basal-like subtype.
  • TP53 mutation typically occurs first in luminal tumors; PIK3CA mutations are rare.
  • Intratumor heterogeneity for wild-type BRCA1 loss and increased proliferation/centrosome amplification observed in normal epithelium of carriers.

Conclusions:

  • The study elucidates the distinct temporal orders of somatic events in different subtypes of BRCA1-associated breast cancer.
  • Findings highlight the importance of considering tumor heterogeneity and early genetic events for treatment strategies.
  • Results provide critical insights for designing chemopreventive and therapeutic interventions for high-risk BRCA1 mutation carriers.