Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes

BMC Genomics
Zhuyi XueInanc Birol

Abstract

Alternative polyadenylation (APA) results in messenger RNA molecules with different 3' untranslated regions (3' UTRs), affecting the molecules' stability, localization, and translation. APA is pervasive and implicated in cancer. Earlier reports on APA focused on 3' UTR length modifications and commonly characterized APA events as 3' UTR shortening or lengthening. However, such characterization oversimplifies the processing of 3' ends of transcripts and fails to adequately describe the various scenarios we observe. We built a cloud-based targeted de novo transcript assembly and analysis pipeline that incorporates our previously developed cleavage site prediction tool, KLEAT. We applied this pipeline to elucidate the APA profiles of 114 genes in 9939 tumor and 729 tissue normal samples from The Cancer Genome Atlas (TCGA). The full set of 10,668 RNA-Seq samples from 33 cancer types has not been utilized by previous APA studies. By comparing the frequencies of predicted cleavage sites between normal and tumor sample groups, we identified 77 events (i.e. gene-cancer type pairs) of tumor-specific APA regulation in 13 cancer types; for 15 genes, such regulation is recurrent across multiple cancers. Our results also support a previous ...Continue Reading

References

Jul 19, 2000·Genome Research·E BeaudoingD Gautheret
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Jan 14, 2005·Nucleic Acids Research·Bin TianCarol S Lutz
Feb 25, 2005·Bioinformatics·Thomas D Wu, Colin K Watanabe
Mar 3, 2009·Genome Research·Jared T SimpsonInanç Birol
Apr 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Zhe JiBin Tian
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Feb 12, 2010·Bioinformatics·Thomas D Wu, Serban Nacu
Oct 12, 2010·Nature Methods·Gordon RobertsonInanc Birol
Oct 30, 2010·Cell·J Robert Hogg, Stephen P Goff
Sep 20, 2011·Molecular Cell·Dafne Campigli Di GiammartinoJames L Manley
Mar 29, 2012·Genome Research·Adnan DertiTomas Babak
Jun 23, 2012·Genome Research·Igor UlitskyDavid P Bartel
May 2, 2013·Trends in Biochemical Sciences·Bin Tian, James L Manley
Jun 19, 2013·Nature Reviews. Genetics·Ran ElkonReuven Agami
Oct 31, 2014·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Apr 22, 2015·Nature·Binyamin D Berkovits, Christine Mayr
Sep 24, 2015·Nature Reviews. Molecular Cell Biology·Søren Lykke-Andersen, Torben Heick Jensen
Nov 26, 2015·Trends in Cell Biology·Christine Mayr
Dec 17, 2015·Circulation Research·Esther E CreemersYigal M Pinto
Apr 15, 2016·Molecular Cancer Research : MCR·Ayse Elif Erson-Bensan, Tolga Can
May 26, 2016·Pflügers Archiv : European journal of physiology·Anton OgorodnikovSven Danckwardt
Jun 25, 2016·Database : the Journal of Biological Databases and Curation·Bronwen L AkenStephen M J Searle
Sep 13, 2016·Nature Genetics·Rik G H LindeboomBen Lehner
Nov 4, 2016·Nature Reviews. Molecular Cell Biology·Bin Tian, James L Manley
Jan 31, 2017·PloS One·Thomas Bonfert, Caroline C Friedel
Nov 3, 2017·Cancer Research·Sheila M ReynoldsIlya Shmulevich

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Citations

Sep 11, 2019·Nucleic Acids Research·Eldad David Shulman, Ran Elkon
Jul 4, 2019·Nature Reviews. Genetics·Andreas J Gruber, Mihaela Zavolan
May 16, 2020·Human Molecular Genetics·Kiel T Tietz, Scott M Dehm
Oct 25, 2019·Genes & Diseases·Fuwen YuanQianben Wang
May 1, 2021·International Journal of Molecular Sciences·Riccardo Di FioreJean Calleja-Agius
Jun 3, 2021·International Journal of Molecular Sciences·Nitika KandhariTraude H Beilharz
Sep 29, 2021·Wiley Interdisciplinary Reviews. RNA·Neeraja K MohananRakesh S Laishram

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Methods Mentioned

BETA
RNA-Seq

Software Mentioned

BioBloom tools
Google Cloud Storage
Seq
COSMIC
Trans
SciPy
BWA
KLEAT
ContextMap
Pandas

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