Related Experiment Video

Updated: May 7, 2026

Comparative Lesions Analysis Through a Targeted Sequencing Approach
08:16

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

6.2K

Somatic copy number changes in DPYD are associated with lower risk of recurrence in triple-negative breast cancers

E Gross1, C Meul, S Raab

  • 1Department of Gynecology and Obstetrics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

British Journal of Cancer
|October 10, 2013
PubMed
Abstract

Insights

Genomic rearrangements in the dihydropyrimidine dehydrogenase gene (DPYD) are common in triple-negative breast cancer (TNBC). These DPYD copy number variations are linked to improved outcomes with 5-FU-based chemotherapy.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Genomic rearrangements at FRA1E can disrupt the dihydropyrimidine dehydrogenase (DPYD) gene, crucial for 5-fluorouracil (5-FU) metabolism.
  • Triple-negative breast cancer (TNBC) often exhibits DNA repair deficiencies, potentially increasing susceptibility to DPYD copy number variations (CNVs).

Purpose of the Study:

  • To investigate the occurrence of DPYD CNVs in TNBC.
  • To evaluate the impact of DPYD CNVs on patient response to standard adjuvant chemotherapy.

Main Methods:

  • DPYD CNVs were analyzed in 106 TNBC tumors using multiplex ligation-dependent probe amplification (MLPA).
  • Dihydropyrimidine dehydrogenase (DPD) protein expression was assessed via immunohistochemistry in 146 TNBC tissues.

Main Results:

  • 41% of TNBC tumors showed DPYD deletions/duplications, associated with higher histological grade and BRCA1 rearrangements.
  • DPYD CNVs correlated with longer time to progression in patients receiving 5-FU- or anthracycline-based chemotherapy, irrespective of DPD protein levels.
  • Patients with DPYD CNVs had a significantly better prognosis (HR=0.26, P=0.023).

Conclusions:

  • Genomic rearrangements in DPYD, not aberrant DPD protein levels, define a tumor profile associated with prolonged response to first-line chemotherapy in TNBC.
  • DPYD CNVs represent a potential predictive biomarker for chemotherapy response in TNBC.

More Related Videos

High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts06:06

High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts

Published on: December 20, 2024

1.3K
Digital Polymerase Chain Reaction Assay for the Genetic Variation in a Sporadic Familial Adenomatous Polyposis Patient Using the Chip-in-a-tube Format05:58

Digital Polymerase Chain Reaction Assay for the Genetic Variation in a Sporadic Familial Adenomatous Polyposis Patient Using the Chip-in-a-tube Format

Published on: August 20, 2018

11.9K

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
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
11.6K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
3.7K
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...
12.7K
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.5K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.0K