Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6

Morgan Thurman; Jacob van Doorn; Barbara Danzer; Thomas R. Webb; Stefan Stamm

doi:10.1177/1177271917730557

Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6

Morgan Thurman, Jacob van Doorn, Barbara Danzer, Thomas R. Webb, Stefan Stamm

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

7 Scopus citations

Abstract

Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction. Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells. Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.

Original language	English
Journal	Biomarker Insights
Volume	12
DOIs	https://doi.org/10.1177/1177271917730557
State	Published - Sep 11 2017

Bibliographical note

Funding Information:
FunDing: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the NIH. (CA140474 and Clinical and Translational Science Award (CTSA) UL1TR001998); BD was supported by a RISE-DAAD fellowship.

Publisher Copyright:
© 2017, © The Author(s) 2017.

Keywords

Alternative splicing
lymphocytes RNA
splicing inhibition
sudemycin

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Biochemistry, medical

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1177/1177271917730557

Cite this

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title = "Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6",

abstract = "Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction. Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells. Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.",

keywords = "Alternative splicing, lymphocytes RNA, splicing inhibition, sudemycin",

author = "Morgan Thurman and {van Doorn}, Jacob and Barbara Danzer and Webb, {Thomas R.} and Stefan Stamm",

note = "Funding Information: FunDing: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the NIH. (CA140474 and Clinical and Translational Science Award (CTSA) UL1TR001998); BD was supported by a RISE-DAAD fellowship. Publisher Copyright: {\textcopyright} 2017, {\textcopyright} The Author(s) 2017.",

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doi = "10.1177/1177271917730557",

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T1 - Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6

AU - Thurman, Morgan

AU - van Doorn, Jacob

AU - Danzer, Barbara

AU - Webb, Thomas R.

AU - Stamm, Stefan

N1 - Funding Information: FunDing: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the NIH. (CA140474 and Clinical and Translational Science Award (CTSA) UL1TR001998); BD was supported by a RISE-DAAD fellowship. Publisher Copyright: © 2017, © The Author(s) 2017.

PY - 2017/9/11

Y1 - 2017/9/11

N2 - Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction. Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells. Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.

AB - Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction. Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells. Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.

KW - Alternative splicing

KW - lymphocytes RNA

KW - splicing inhibition

KW - sudemycin

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VL - 12

JO - Biomarker Insights

JF - Biomarker Insights

ER -

Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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