Related Experiment Video
Updated: Feb 8, 2026
07:25
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
13.9K
Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing
Srinivas R Viswanathan1, Gavin Ha1, Andreas M Hoff2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Cell
|June 19, 2018
Summary
Metastatic castration-resistant prostate cancer (mCRPC) shows frequent AR locus rearrangements, including tandem duplications of an AR enhancer, unlike primary prostate cancers. These findings reveal complex mCRPC genomics and potential therapeutic targets.
Area of Science:
- Genomics
- Oncology
- Prostate Cancer Research
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) is the primary cause of prostate cancer mortality.
- Limited whole-genome sequencing (WGS) studies exist for mCRPC, hindering understanding of its genomic landscape.
- Identifying genomic alterations in mCRPC is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the genomic architecture of mCRPC using whole-genome sequencing.
- To identify recurrent genetic alterations, particularly in the non-coding regions, associated with mCRPC progression.
- To discover potential therapeutic targets for mCRPC based on novel genomic findings.
Main Methods:
- Performed linked-read whole-genome sequencing (WGS) on 23 mCRPC biopsy specimens.
- Analyzed cell-free DNA (cfDNA) sequencing data from 86 mCRPC patients.
- Characterized complex genomic rearrangements, focusing on the AR locus and enhancer regions.
Main Results:
- Observed frequent and complex rearrangements of the AR locus in most mCRPC cases.
- Discovered highly recurrent tandem duplications of an AR upstream enhancer in 70%-87% of mCRPC cases, significantly higher than in primary prostate cancers (<2%).
- Identified a subset of cases with AR or MYC enhancer duplication linked to a genome-wide tandem duplicator phenotype driven by CDK12 inactivation.
Conclusions:
- The study reveals a complex and distinct genomic structure in mCRPC, particularly involving AR locus rearrangements.
- Recurrent enhancer duplications represent potential novel therapeutic targets for mCRPC treatment.
- Further exploration of the non-coding mCRPC genome may uncover additional recurrent events and therapeutic strategies.
Related Concept Videos
02:02Genomics
40.8K
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...
40.8K
02:56Treatment Resistant Cancers
3.8K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
02:04Covalently Linked Protein Regulators
9.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.7K
01:26Size and Structure of Viral Genomes
807
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
807
02:30Genomic Imprinting and Inheritance
37.2K
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...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.2K
03:21Genome Size and the Evolution of New Genes
9.2K
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