Analysis of the "centrosome-ome" identifies MCPH1 deletion as a cause of centrosome amplification in human cancer.

Scientific Reports
Ryan A Denu, Mark E Burkard

Abstract

The centrosome is the microtubule organizing center of human cells and facilitates a myriad of cellular functions including organization of the mitotic spindle to ensure faithful chromosome segregation during mitosis, cell polarization and migration, and primary cilia formation. A numerical increase in centrosomes, or centrosome amplification (CA), is common in cancer and correlates with more aggressive clinical features and worse patient outcomes. However, the causes of CA in human cancer are unclear. Many previous studies have identified mechanisms of CA in cellulo, such as overexpression of PLK4, but it is unclear how often these are the primary mechanism in human disease. To identify a primary cause of CA, we analyzed The Cancer Genome Atlas (TCGA) genomic and transcriptomic data for genes encoding the 367 proteins that localize to the centrosome (the "centrosome-ome"). We identified the following candidates for primary causes of CA: gain-of-function alterations of CEP19, CEP72, CTNNB1, PTK2, NDRG1, SPATC1, TBCCD1; and loss-of-function alterations of CEP76, MCPH1, NEURL4, and NPM1. In cellulo analysis of these candidates revealed that loss of MCPH1/microcephalin caused the most robust increase in centriole number. MCPH1 dee...Continue Reading

References

Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·N R RodriguesD P Lane
Jul 3, 2003·Cell·Shiaw Yih Lin, Stephen J Elledge
Jun 29, 2004·The Journal of Biological Chemistry·Xingzhi XuDavid F Stern
Oct 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Shiaw-Yih LinStephen J Elledge
Jun 20, 2006·Nature Cell Biology·Gemma K AldertonMark O'Driscoll
Jan 30, 2007·Carcinogenesis·Ignacio Pérez de CastroMarcos Malumbres
Jun 2, 2009·Current Biology : CB·Thorsten I SchmidtErich A Nigg
Jun 24, 2009·The Journal of Cell Biology·Alexandra TibeliusAlwin Krämer
Nov 17, 2009·Cell·Erich A Nigg, Jordan W Raff
Dec 24, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander T El GammalThorsten Schlomm
Jul 16, 2010·Breast Cancer Research and Treatment·Julie RichardsonSandra M Bell
Jul 28, 2010·Oncogene·J A L BrownC G Morrison
Apr 21, 2011·British Journal of Cancer·A Brüning-RichardsonS M Bell
Nov 2, 2011·International Journal of Biological Sciences·Jason Yongsheng Chan
Apr 18, 2014·Nature·Susana A GodinhoDavid Pellman
Jul 23, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·S A Godinho, D Pellman
Jun 24, 2015·The Journal of Cell Biology·Tyler C MoyerAndrew J Holland
Oct 24, 2015·Nature Reviews. Cancer·Pierre Gönczy
Nov 21, 2015·Molecular Cancer Therapeutics·Alka ChoudharyMark E Burkard
Jul 20, 2016·The Journal of Cell Biology·Bramwell G LambrusAndrew J Holland
Jan 20, 2017·PLoS Genetics·Nina PeelKevin F O'Connell
Jan 29, 2017·Genes & Development·Luca L FavaAndreas Villunger
Jan 14, 2018·Molecular Cancer Research : MCR·Ryan A DenuNihal Ahmad

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Datasets Mentioned

BETA
CHIR-124
MHS6278-202828648

Methods Mentioned

BETA
transfection
PCR
ubiquitination
exome sequencing

Software Mentioned

Prism Graphpad
SuperPlots
Excel
cBioPortal
MutSigCV
ImageJ

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