The Genomic Landscape of Centromeres in Cancers

Scientific Reports
Anjan K SahaRafael Contreras-Galindo

Abstract

Centromere genomics remain poorly characterized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centromeric loci difficult to achieve. We here leverage a highly specific and targeted rapid PCR methodology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centromeric core and pericentromeric markers (α-satellite units and HERV-K copies) were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric endogenous retrovirus amplified by PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent a more comprehensive evaluation of centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression.

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Citations

Jun 12, 2019·The New Phytologist·Thibault LeroyAntoine Kremer
Oct 21, 2019·The New Phytologist·Antoine Kremer, Andrew L Hipp
Nov 28, 2019·The New Phytologist·Marion O Harris, Andrea Pitzschke
Dec 15, 2020·Science Advances·Yuta SuzukiShinichi Morishita
Aug 28, 2021·International Journal of Molecular Sciences·Laura Leo, Nunzia Colonna Romano
Oct 6, 2021·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Yuta Suzuki, Shinichi Morishita

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Methods Mentioned

BETA
PCR

Software Mentioned

gplots
plotrix
RColorBrewer
BioEdit
R
MrBayes
BLAST
RStudio
MEGA5

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