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Printable Handouts
Navigable Slide Index
- Introduction
- Topics
- Accumulation of multiple genomic alterations is a common feature of the cancer genomes
- Complexity of genomic alterations: SNV & Indel
- Complexity of genomic alterations: structural variation
- Complexity of genomic alterations: CIN
- Cancer: combined consequence of accumulations of genomic alterations & clonal expansion
- Accurate segregation of chromosomes
- Chromosome segregation and genomic instability
- Cell cycle coordination
- Cell cycle coordination and genomic integrity
- Fidelity of DNA replication
- Potential sources of errors during DNA replication
- Fidelity of DNA replication: errors from DNA polymerases
- Some mismatches remain after DNA duplication
- The strand-specificity of MMR in mammalian cells
- Replication slippage and microsatellite instability
- Fidelity of DNA replication: telomere stability and length
- Obstacle of stalled/broken replication forks
- Accumulation of DNA replication errors as cells proliferate
- Precise repair of DNA damage
- Genomic instability caused by DNA damage and imprecise repair
- BER and repair of depurination or depyrimidination sites and SSB
- Nucleotide excision repair (NER)
- DSB repair by non-homologous end-joining (NHEJ)
- DSB repair: homologous recombinational repair
- Single strand anneal (SSA)
- Repair of double strand breaks (DSB)
- Resolution of stalled/broken replication forks
- HR machinery is critical
- DNA damage processing defects & human diseases
- Important concepts about DNA repair pathways
- Base excision repair (BER) (1)
- The concept of synthetic lethality
- Base excision repair (BER) (2)
- BRCAness and its targeting strategies
- Treatment of BRCAness tumors by PARP inhibitor
- Mechanism of action by PARPi: inhibitor or poison?
- Topics review
Topics Covered
- Genomic alterations in cancer
- Key mechanisms to maintain genome integrity
- The concept of synthetic lethality
- Exploiting DNA repair mechanisms for cancer therapy
- PARP inhibitors
Talk Citation
Shen, Z. (2024, February 29). Genomic instability and cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/TLDM6122.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
Other Talks in the Series: The Molecular Basis of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Hello. Welcome to this
introductory lecture
on Genomic Instability
and Cancer.
My name is Zhiyuan Shen,
I'm a professor at
the Rutgers Robert Wood
Johnson Medical School.
I'm also the Associate
Director for
Basic Research at
the Rutgers Cancer
Institute of New Jersey.
Today, I'm excited to introduce
the topic of genomic
instability and cancer.
0:28
I hope to cover four topics.
I will go over the
general features and
the key mechanisms that
help to maintain the
genomic integrity,
then briefly talk
about the concept of
synthetic lethality
and to exploit
DNA repair mechanisms for
the treatment of cancer.
0:50
First of all, why do we need
to talk about genomic
instability in cancer?
It turns out and
not surprisingly,
that cancers often have
accumulated multiple genomic
alterations in the genomes.
As shown in this table
published about 10 years ago,
one can already observe
multiple mutations in
different cancer types simply by
examining X and sequences
of the coding genes.
When talking about genomic
alterations on mutations,
we should keep in mind that
some mutations are drivers
that can directly lead to
the cancer growth and
survival advantages.
But perhaps more are
just passenger
mutations that might
not directly contribute
to the growth advantage,
but they can reveal
the genomic basis of
cancer evolution and
cancer vulnerability
to selective therapy.