Genomic Evolution and Transcriptional Changes in the Evolution of Prostate Cancer into Neuroendocrine and Ductal Carcinoma Types

Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de...

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Published in:International journal of molecular sciences Vol. 24; no. 16; p. 12722
Main Authors: Rao, Srinivasa R., Protheroe, Andrew, Cerundolo, Lucia, Maldonado-Perez, David, Browning, Lisa, Lamb, Alastair D., Bryant, Richard J., Mills, Ian G., Woodcock, Dan J., Hamdy, Freddie C., Tomlinson, Ian P. M., Verrill, Clare
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 12.08.2023
MDPI
Subjects:
Analysis
Androgen Antagonists
Androgens
Cancer
Carcinoma
Carcinoma, Acinar Cell
Carcinoma, Ductal - genetics
Carcinoma, Small Cell
Evolution, Molecular
Gene amplification
Gene expression
Genetic aspects
Genetic transcription
Genomes
Genomics
Humans
Lung Neoplasms
Male
Morphology
Mutation
Neuroendocrine tumors
Patients
Phylogenetics
Phylogeny
Prostate cancer
Prostatic Neoplasms - genetics
Small Cell Lung Carcinoma
Tumor proteins
United Kingdom
whole genome duplication
genomics
prostate cancer
tumor evolution
neuroendocrine
small cell
ISSN:1422-0067, 1661-6596, 1422-0067
Online Access:Get full text
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Summary:Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tissue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with three longitudinal samples over 5 years. Case 2 was a single time point after the development of treatment-related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all samples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, and 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small-cell neuroendocrine and ductal prostatic carcinoma can have a common ancestry. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241612722