Related Experiment Video

Updated: Feb 13, 2026

Characterization of a Pathogenic Escherichia coli Strain Derived from Oreochromis spp. Farms Using Whole-Genome Sequencing
09:44

Characterization of a Pathogenic Escherichia coli Strain Derived from Oreochromis spp. Farms Using Whole-Genome Sequencing

Published on: December 23, 2022

3.0K

Characterization of Camptothecin-induced Genomic Changes in the Camptothecin-resistant T-ALL-derived Cell Line CPT-K5

Eigil Kjeldsen1, Christine J F Nielsen2, Amit Roy2

  • 1Cancer Cytogenetics Section, HemoDiagnostic Laboratory, Aarhus University Hospital, Aarhus, Denmark Eigil.Kjeldsen@clin.au.dk.

Cancer Genomics & Proteomics
|March 3, 2018
PubMed

Insights

Drug resistance to topoisomerase I (TOP1) inhibitors involves significant genomic changes. This study reveals that short tandem repeats are DNA targets for TOP1, influencing camptothecin resistance.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Genetics

Background:

  • Acquiring resistance to topoisomerase I (TOP1)-targeting camptothecin (CPT) derivatives presents a significant clinical challenge.
  • The chromosomal and genomic mechanisms underlying this resistance are not well understood.

Purpose of the Study:

  • To characterize the genomic and chromosomal alterations in a CPT-resistant cell line (CPT-K5) compared to its CPT-sensitive parental line (RPMI-8402).
  • To investigate the role of short tandem repeats (STRs) in TOP1-mediated DNA damage and CPT resistance.

Main Methods:

  • Karyotyping to analyze chromosomal structure and number.
  • Subtractive oligo-based array comparative genomic hybridization (soaCGH) to detect copy number alterations and DNA breakpoints.
  • Short tandem repeat (STR) analysis to assess allelic differences.

Main Results:

  • CPT-K5 cells exhibited additional structural chromosomal aberrations and a reduced modal chromosome number compared to RPMI-8402.
  • soaCGH identified extensive copy number alterations and over 200 unbalanced DNA breakpoints in CPT-K5.
  • Significant differences in STR alleles were observed between the two cell lines.
  • Copy number alterations affected genes crucial for genome integrity and DNA damage repair.
  • Short tandem repeats were identified as direct targets of TOP1 cleavage, with differential stimulation by CPT.

Conclusions:

  • Topoisomerase I (TOP1) inhibitor resistance is associated with substantial genomic instability and chromosomal aberrations.
  • Short tandem repeats (STRs) are novel targets for TOP1 cleavage and play a role in the development of camptothecin (CPT) resistance.
Keywords:
CPT-K5aCGHcamptothecin resistancegenomic instabilitykaryotypeshort tandem repeat

More Related Videos

Derivation and Characterization of a Transgene-free Human Induced Pluripotent Stem Cell Line and Conversion into Defined Clinical-grade Conditions10:48

Derivation and Characterization of a Transgene-free Human Induced Pluripotent Stem Cell Line and Conversion into Defined Clinical-grade Conditions

Published on: November 26, 2014

8.3K
Derivation, Expansion, Cryopreservation and Characterization of Brain Microvascular Endothelial Cells from Human Induced Pluripotent Stem Cells08:04

Derivation, Expansion, Cryopreservation and Characterization of Brain Microvascular Endothelial Cells from Human Induced Pluripotent Stem Cells

Published on: November 19, 2020

7.1K

Related Concept Videos

Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.3K
Genomics02:02

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
40.9K
Genome Size and the Evolution of New Genes03:21

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
9.2K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.1K
Resistivity01:22

Resistivity

When a voltage is applied to a conductor, an electrical field is generated, and charges in the conductor feel the force due to the electrical field. The current density that results depends on the electrical field and the properties of the material. In some materials, including metals at a given temperature, the current density is approximately proportional to the electrical field. In these cases, the current density can be modeled as:
4.6K
Resistance01:19

Resistance

When a current moves through any conductor, the conductor causes some level of difficulty for the current to flow. The measure of that difficulty is known as the resistance of the material and is represented by R. Every material has its own resistance. In the case of conductors, heat is emitted whenever a current passes through them. Resistance depends on the resistivity of the material. Resistivity is a characteristic of the material used to fabricate electrical components, whereas the...
6.1K