Poly‐gene fusion transcripts and chromothripsis in prostate cancer
Abstract
Complex genome rearrangements are frequently observed in cancer but their impact on tumor molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumors exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly‐gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly‐gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumor with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data show that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly‐gene fusion transcripts is potentially of great significance to cancer genetics. © 2012 Wiley Periodicals, Inc.
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Transiently expressed genomic breakpoint sequences that are associated with real gene fusions often overlap transposons.
“Transiently expressed genomic breakpoint sequences that are associated with real gene fusions often overlap transposons; these should be filtered unless they are associated with additional fusion isoforms from the same gene pair [89].”
From A survey of best practices for RNA-seq data analysis (2016) · cites this paper as [89]
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Bioresource, A. P. C., Lai, J., An, J., Seim, I., Walpole, C., Hoffman, A., Moya, L., Srinivasan, S., Perry‐Keene, J., Wang, C., et al. (2015) · BMC Genomics · doi:10.1186/s12864-015-2235-4 · Cited by 16 · see citing works
“Interestingly, some of these chromosomal rearrangement fusion genes can produce fusion transcripts comprising exons from more than two genes [11].”
BackgroundIdentifying the oncogenic potential of gene fusions exploiting miRNAs
Lovino, M., Montemurro, M., Barrese, V. S., & Ficarra, E. (2022) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2022.104057 · Cited by 16 · see citing works
Systematic Identification and Characterization of RNA Editing in Prostate Tumors
Mo, F., Wyatt, A. W., Sun, Y., Brahmbhatt, S., McConeghy, B. J., Wu, C., Wang, Y. Z., Gleave, M. E., Volik, S. V., & Collins, C. C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101431 · Cited by 15 · see citing works
“This data spanned 10 prostatic tumors from primary and metastatic sites of 6 patients [50,51,52], 2 cell lines (LNCaP and C42) [50], and 2 patient derived xenograft tumors from 1 patient [53,54].”
BackgroundSelf-citationThe yin and yang of chromosomal instability in prostate cancer
Carceles‐Cordon, M., Orme, J. J., Domenech, J. M. D., & Rodríguez-Bravo, V. (2024) · Nature Reviews Urology · doi:10.1038/s41585-023-00845-9 · Cited by 13 · see citing works
“This emerging body of functional and molecular analyses regarding the role of CIN levels in both primary and metastatic tumours elucidates some of the causes, consequences and prevalence of CIN in prostate cancer 108 .”
Chromoplexy: a new paradigm in genome remodeling and evolution
Wang, K., Wang, Y. Z., & Collins, C. C. (2013) · Asian Journal of Andrology · doi:10.1038/aja.2013.109 · Cited by 12 · see citing works
Self-citationConstitutional chromothripsis involving chromosome 19 in a child with subtle dysmorphic features
Wang, J., Fisker, T., & Sahoo, T. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36962 · Cited by 11 · see citing works
“, 2011b], prostate cancer [Wu et al., 2012], glioblastoma [Zack et al.”
BackgroundTeng, P., Huang, S., Liu, C.-H., Lin, T.-Y., Cho, Y.-C., Lai, Y.-L., Wang, S., Yeh, H., Chuu, C., Chen, D., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111771 · Cited by 11 · see citing works
Prostate Cancer Genomic Subtypes
Fraser, M. E., & Rouette, A. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-32656-2_5 · Cited by 11 · see citing works
Chromothripsis and Human Genetic Disease
Nazaryan‐Petersen, L., & Tommerup, N. (2016) · Wiley eBooks · doi:10.1002/9780470015902.a0024627 · Cited by 11 · see citing works
Cai, H. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7780-2_18 · Cited by 7 · see citing works
Chromothripsis in Oncology: Literature Review and Case Report
Nn, M., Gindina, T., & Бойченко, Э. Г. (2017) · Clinical oncohematology · doi:10.21320/2500-2139-2017-10-2-191-205 · Cited by 5 · see citing works
“Молекулярно-биологических исследований, направленных на выявление и характеристику хромотрипсиса при раке простаты, пока немного [11, 59].”
Genomic landscaping of receptor tyrosine kinase ALK with highly frequent rearrangements in cancers
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“35 Additionally, specific chromosomal or DNA structures have been identified as contributing factors in the generation of gene fusions.”
RNA-Seq Analysis to Detect Abnormal Fusion Transcripts Linked to Chromothripsis
Bougé, A.-L., Rufflé, F., Riquier, S., Guibert, B., Audoux, J., & Commes, T. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7780-2_9 · Cited by 2 · see citing works
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Phan, M., Gomes, M. A., Stinnett, V., Morsberger, L. A., Hoppman, N. L., Pearce, K. E., Smith, K., Phan, B., Jiang, L., & Zou, Y. S. (2024) · Biomedicines · doi:10.3390/biomedicines12030598 · Cited by 2 · see citing works
Large-scale data analysis to identify novel disease phenotypes and genes
Kaasinen, E. (2014) · Työväentutkimus Vuosikirja
Yeung, J. (2014) · cIRcle (University of British Columbia) · doi:10.14288/1.0167443
“Genetic alterations in PCa involves large-scale genomic rearrangements and copy number changes across multiple chromosomes, a phenomenon called chromoplexy [6, 91, 112].”
BackgroundPotential use of Aneustat for improvement of docetaxel-based therapy of advanced prostate cancer
Qu, S. (2017) · cIRcle (University of British Columbia) · doi:10.14288/1.0357970
“The LTL-313H prostate cancer tissue xenograft line used in this study is deficient in PTEN [370] and the finding that treatment of the xenografts with docetaxel+Aneustat, as distinct from the single agents, led to complete inhibition of tumor growth coupled to tumor shrinkage, is consistent with inhibition of both AR…”
MethodRatz (2017) · doi:10.26481/dis.20171215lr
Identifying the oncogenic potential of gene fusions exploiting miRNAsPreprint
Barrese, V. S., Montemurro, M., Lovino, M., & Ficarra, E. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.20.465128
Neue präklinische Modelle und Biomarker beim Prostatakarzinom
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Targeting the genes of 9p13.3 amplicon in prostate cancer
Grönlund, T. (2015) · Tampere University Institutional Repository (Tampere University)
- Authors
- Wu, C., Wyatt, A. W., McPherson, A., Lin, D., McConeghy, B. J., Mo, F., Shukin, R., Lapuk, A. V., M. Jones, S. J., Zhao, Y., Marra, M. A., Gleave, M. E., Volik, S. V., Wang, Y., Sahinalp, S. C., & Collins, C. C.
- Affiliations
- University of British Columbia (CA)
- Simon Fraser University (CA)
- BC Cancer Agency (CA)
- Corresponding author
- Collins, Colin C.
- ORCID
- Venue
- Genes, Chromosomes and Cancer
- Publisher
- Wiley
- Published
- 2012-08-25
- Volume
- 51
- Issue
- 12
- Pages
- 1144-1153
- ISSN
- 1045-2257 (ISSN-L)
- 1098-2264
- OpenAlex
- W2023006132
- Cited by
- 51
- References
- 51
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 11 · 2013: 11 · 2012: 2
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Chromosomes and Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- chromothripsis, prostate cancer, LNCaP cells, TP53 mutation, DNA damage response, cancer genetics
- MeSH terms
- Chromosome Aberrations, Humans, Male, Mutation, Prostatic Neoplasms, Cell Line, Tumor, Gene Fusion
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