DOI: 10.1101/505800Dec 25, 2018Paper

The Genomic Landscape of Centromeres in Cancers

BioRxiv : the Preprint Server for Biology
Anjan 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.

Related Concepts

Malignant Neoplasms
Centromere
DNA, Satellite
Biological Evolution
Genes
Neoplasms
Polymerase Chain Reaction
Retroviridae
Tumor Markers, Biological
Cell Line, Tumor

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