CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue

Job van Riet; Chinmoy Saha; Nikolaos Strepis; Rutger W.W. Brouwer; Elena S. Martens-Uzunova; Wesley S. van de Geer; Sigrid M.A. Swagemakers; Andrew Stubbs; Yassir Halimi; Sanne Voogd; Arif Mohammad Tanmoy; Malgorzata A. Komor; Youri Hoogstrate; Bart Janssen; Remond J.A. Fijneman; Yashar S. Niknafs; Arul M. Chinnaiyan; Wilfred F.J. van IJcken; Peter J. van der Spek; Guido Jenster; Rogier Louwen

doi:10.1038/s42003-022-03249-4

CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue

Job van Riet, Chinmoy Saha, Nikolaos Strepis, Rutger W.W. Brouwer, Elena S. Martens-Uzunova, Wesley S. van de Geer, Sigrid M.A. Swagemakers, Andrew Stubbs, Yassir Halimi, Sanne Voogd, Arif Mohammad Tanmoy, Malgorzata A. Komor, Youri Hoogstrate, Bart Janssen, Remond J.A. Fijneman, Yashar S. Niknafs, Arul M. Chinnaiyan, Wilfred F.J. van IJcken, Peter J. van der Spek, Guido JensterRogier Louwen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been identified in bacteria, archaea and mitochondria of plants, but not in eukaryotes. Here, we report the discovery of 12,572 putative CRISPRs randomly distributed across the human chromosomes, which we termed hCRISPRs. By using available transcriptome datasets, we demonstrate that hCRISPRs are distinctively expressed as small non-coding RNAs (sncRNAs) in cell lines and human tissues. Moreover, expression patterns thereof enabled us to distinguish normal from malignant tissues. In prostate cancer, we confirmed the differential hCRISPR expression between normal adjacent and malignant primary prostate tissue by RT-qPCR and demonstrate that the SHERLOCK and DETECTR dipstick tools are suitable to detect these sncRNAs. We anticipate that the discovery of CRISPRs in the human genome can be further exploited for diagnostic purposes in cancer and other medical conditions, which certainly will lead to the development of point-of-care tests based on the differential expression of the hCRISPRs.

Original language	English
Article number	338
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03249-4
Publication status	Published - 8 Apr 2022

Bibliographical note

Funding Information:
C.S. is a graduate student at Erasmus Postgraduate School of Molecular Medicine and is partially supported by I&I Fund (Erasmus Vrienden Fonds). The bioinformatics team of P.J.v.d.S. receives supporting funding from H2020 projects ImmuneAID and Moodstratification for Data analysis infrastructure. Moreover, national funding has been obtained from the ZonMW project Genomes First for genomics infrastructure. The team of R.L. receives supporting funding from H2020 project STAMINA (ID: 883441), the Chiron Foundation and by PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships LSH-TKI foundation grant LSHM18006. Prostate RNA-seq data were generated within the framework of the CTMM research program, project NGS‐ProToCol (grant 03 O‐402). We acknowledge Rene Akre for critical reading and editing the manuscript. Finally, we would like to pay our deepest respect to Prof. Johan W. Mouton, who passed away on the 9 July 2019 due to complications caused by prostate cancer ( https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30441-4/fulltext ). Prof. Mouton was supervisor of author and PhD student Chinmoy Saha, thanks to his support, guidance, motivation and scientific advice this work might form the basis to improve prostate cancer diagnostics and prognostics.

Publisher Copyright:
© 2022, The Author(s).

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CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissueFinal published version, 29.3 MBLicence: CC BY

Cite this

van Riet, J., Saha, C., Strepis, N., Brouwer, R. W. W., Martens-Uzunova, E. S., van de Geer, W. S., Swagemakers, S. M. A., Stubbs, A., Halimi, Y., Voogd, S., Tanmoy, A. M., Komor, M. A., Hoogstrate, Y., Janssen, B., Fijneman, R. J. A., Niknafs, Y. S., Chinnaiyan, A. M., van IJcken, W. F. J., van der Spek, P. J., ... Louwen, R. (2022). CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue. Communications Biology, 5(1), Article 338. https://doi.org/10.1038/s42003-022-03249-4

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title = "CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue",

abstract = "Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been identified in bacteria, archaea and mitochondria of plants, but not in eukaryotes. Here, we report the discovery of 12,572 putative CRISPRs randomly distributed across the human chromosomes, which we termed hCRISPRs. By using available transcriptome datasets, we demonstrate that hCRISPRs are distinctively expressed as small non-coding RNAs (sncRNAs) in cell lines and human tissues. Moreover, expression patterns thereof enabled us to distinguish normal from malignant tissues. In prostate cancer, we confirmed the differential hCRISPR expression between normal adjacent and malignant primary prostate tissue by RT-qPCR and demonstrate that the SHERLOCK and DETECTR dipstick tools are suitable to detect these sncRNAs. We anticipate that the discovery of CRISPRs in the human genome can be further exploited for diagnostic purposes in cancer and other medical conditions, which certainly will lead to the development of point-of-care tests based on the differential expression of the hCRISPRs.",

author = "{van Riet}, Job and Chinmoy Saha and Nikolaos Strepis and Brouwer, {Rutger W.W.} and Martens-Uzunova, {Elena S.} and {van de Geer}, {Wesley S.} and Swagemakers, {Sigrid M.A.} and Andrew Stubbs and Yassir Halimi and Sanne Voogd and Tanmoy, {Arif Mohammad} and Komor, {Malgorzata A.} and Youri Hoogstrate and Bart Janssen and Fijneman, {Remond J.A.} and Niknafs, {Yashar S.} and Chinnaiyan, {Arul M.} and {van IJcken}, {Wilfred F.J.} and {van der Spek}, {Peter J.} and Guido Jenster and Rogier Louwen",

note = "Funding Information: C.S. is a graduate student at Erasmus Postgraduate School of Molecular Medicine and is partially supported by I&I Fund (Erasmus Vrienden Fonds). The bioinformatics team of P.J.v.d.S. receives supporting funding from H2020 projects ImmuneAID and Moodstratification for Data analysis infrastructure. Moreover, national funding has been obtained from the ZonMW project Genomes First for genomics infrastructure. The team of R.L. receives supporting funding from H2020 project STAMINA (ID: 883441), the Chiron Foundation and by PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships LSH-TKI foundation grant LSHM18006. Prostate RNA-seq data were generated within the framework of the CTMM research program, project NGS‐ProToCol (grant 03 O‐402). We acknowledge Rene Akre for critical reading and editing the manuscript. Finally, we would like to pay our deepest respect to Prof. Johan W. Mouton, who passed away on the 9 July 2019 due to complications caused by prostate cancer ( https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30441-4/fulltext ). Prof. Mouton was supervisor of author and PhD student Chinmoy Saha, thanks to his support, guidance, motivation and scientific advice this work might form the basis to improve prostate cancer diagnostics and prognostics. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = apr,

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doi = "10.1038/s42003-022-03249-4",

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van Riet, J, Saha, C , Strepis, N, Brouwer, RWW, Martens-Uzunova, ES , van de Geer, WS , Swagemakers, SMA , Stubbs, A, Halimi, Y, Voogd, S, Tanmoy, AM, Komor, MA, Hoogstrate, Y, Janssen, B, Fijneman, RJA, Niknafs, YS, Chinnaiyan, AM, van IJcken, WFJ, van der Spek, PJ , Jenster, G & Louwen, R 2022, 'CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue', Communications Biology, vol. 5, no. 1, 338. https://doi.org/10.1038/s42003-022-03249-4

TY - JOUR

T1 - CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue

AU - van Riet, Job

AU - Saha, Chinmoy

AU - Strepis, Nikolaos

AU - Brouwer, Rutger W.W.

AU - Martens-Uzunova, Elena S.

AU - van de Geer, Wesley S.

AU - Swagemakers, Sigrid M.A.

AU - Stubbs, Andrew

AU - Halimi, Yassir

AU - Voogd, Sanne

AU - Tanmoy, Arif Mohammad

AU - Komor, Malgorzata A.

AU - Hoogstrate, Youri

AU - Janssen, Bart

AU - Fijneman, Remond J.A.

AU - Niknafs, Yashar S.

AU - Chinnaiyan, Arul M.

AU - van IJcken, Wilfred F.J.

AU - van der Spek, Peter J.

AU - Jenster, Guido

AU - Louwen, Rogier

N1 - Funding Information: C.S. is a graduate student at Erasmus Postgraduate School of Molecular Medicine and is partially supported by I&I Fund (Erasmus Vrienden Fonds). The bioinformatics team of P.J.v.d.S. receives supporting funding from H2020 projects ImmuneAID and Moodstratification for Data analysis infrastructure. Moreover, national funding has been obtained from the ZonMW project Genomes First for genomics infrastructure. The team of R.L. receives supporting funding from H2020 project STAMINA (ID: 883441), the Chiron Foundation and by PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships LSH-TKI foundation grant LSHM18006. Prostate RNA-seq data were generated within the framework of the CTMM research program, project NGS‐ProToCol (grant 03 O‐402). We acknowledge Rene Akre for critical reading and editing the manuscript. Finally, we would like to pay our deepest respect to Prof. Johan W. Mouton, who passed away on the 9 July 2019 due to complications caused by prostate cancer ( https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30441-4/fulltext ). Prof. Mouton was supervisor of author and PhD student Chinmoy Saha, thanks to his support, guidance, motivation and scientific advice this work might form the basis to improve prostate cancer diagnostics and prognostics. Publisher Copyright: © 2022, The Author(s).

PY - 2022/4/8

Y1 - 2022/4/8

N2 - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been identified in bacteria, archaea and mitochondria of plants, but not in eukaryotes. Here, we report the discovery of 12,572 putative CRISPRs randomly distributed across the human chromosomes, which we termed hCRISPRs. By using available transcriptome datasets, we demonstrate that hCRISPRs are distinctively expressed as small non-coding RNAs (sncRNAs) in cell lines and human tissues. Moreover, expression patterns thereof enabled us to distinguish normal from malignant tissues. In prostate cancer, we confirmed the differential hCRISPR expression between normal adjacent and malignant primary prostate tissue by RT-qPCR and demonstrate that the SHERLOCK and DETECTR dipstick tools are suitable to detect these sncRNAs. We anticipate that the discovery of CRISPRs in the human genome can be further exploited for diagnostic purposes in cancer and other medical conditions, which certainly will lead to the development of point-of-care tests based on the differential expression of the hCRISPRs.

AB - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been identified in bacteria, archaea and mitochondria of plants, but not in eukaryotes. Here, we report the discovery of 12,572 putative CRISPRs randomly distributed across the human chromosomes, which we termed hCRISPRs. By using available transcriptome datasets, we demonstrate that hCRISPRs are distinctively expressed as small non-coding RNAs (sncRNAs) in cell lines and human tissues. Moreover, expression patterns thereof enabled us to distinguish normal from malignant tissues. In prostate cancer, we confirmed the differential hCRISPR expression between normal adjacent and malignant primary prostate tissue by RT-qPCR and demonstrate that the SHERLOCK and DETECTR dipstick tools are suitable to detect these sncRNAs. We anticipate that the discovery of CRISPRs in the human genome can be further exploited for diagnostic purposes in cancer and other medical conditions, which certainly will lead to the development of point-of-care tests based on the differential expression of the hCRISPRs.

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