Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells

Somatic DNA hypomethylation and aneuploidy are hallmarks of cancer, and there is evidence for a causal relationship between them in knockout mice but not in human cancer. The non-mobile pericentromeric repetitive elements SST1 are hypomethylated in about 17% of human colorectal cancers (CRC) with so...

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Autores principales:	Beatriz González, Maria Navarro-Jiménez, María José Alonso-De Gennaro, Sanne Marcia Jansen, Isabel Granada, Manuel Perucho, Sergio Alonso
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	genomic DNA hypomethylation colorectal cancer tetraploidization chromosome instability repetitive elements polyploidy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1273cbe6e959447fbfd2d9c82c722e6c
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spelling	oai:doaj.org-article:1273cbe6e959447fbfd2d9c82c722e6c2021-11-11T15:28:53ZSomatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells10.3390/cancers132153532072-6694https://doaj.org/article/1273cbe6e959447fbfd2d9c82c722e6c2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5353https://doaj.org/toc/2072-6694Somatic DNA hypomethylation and aneuploidy are hallmarks of cancer, and there is evidence for a causal relationship between them in knockout mice but not in human cancer. The non-mobile pericentromeric repetitive elements SST1 are hypomethylated in about 17% of human colorectal cancers (CRC) with some 5–7% exhibiting strong age-independent demethylation. We studied the frequency of genome doubling, a common event in solid tumors linked to aneuploidy, in randomly selected single cell clones of near-diploid LS174T human CRC cells differing in their level of SST1 demethylation. Near-diploid LS174T cells underwent frequent genome-doubling events generating near-tetraploid clones with lower levels of SST1 methylation. In primary CRC, strong SST1 hypomethylation was significantly associated with global genomic hypomethylation and mutations in <i>TP53</i>. This work uncovers the association of the naturally occurring demethylation of the SST1 pericentromeric repeat with the onset of spontaneous tetraploidization in human CRC cells in culture and with <i>TP53</i> mutations in primary CRCs. Altogether, our findings provide further support for an oncogenic pathway linking somatic hypomethylation and genetic copy number alterations in a subset of human CRC.Beatriz GonzálezMaria Navarro-JiménezMaría José Alonso-De GennaroSanne Marcia JansenIsabel GranadaManuel PeruchoSergio AlonsoMDPI AGarticlegenomic DNA hypomethylationcolorectal cancertetraploidizationchromosome instabilityrepetitive elementspolyploidyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5353, p 5353 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	genomic DNA hypomethylation colorectal cancer tetraploidization chromosome instability repetitive elements polyploidy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	genomic DNA hypomethylation colorectal cancer tetraploidization chromosome instability repetitive elements polyploidy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Beatriz González Maria Navarro-Jiménez María José Alonso-De Gennaro Sanne Marcia Jansen Isabel Granada Manuel Perucho Sergio Alonso Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
description	Somatic DNA hypomethylation and aneuploidy are hallmarks of cancer, and there is evidence for a causal relationship between them in knockout mice but not in human cancer. The non-mobile pericentromeric repetitive elements SST1 are hypomethylated in about 17% of human colorectal cancers (CRC) with some 5–7% exhibiting strong age-independent demethylation. We studied the frequency of genome doubling, a common event in solid tumors linked to aneuploidy, in randomly selected single cell clones of near-diploid LS174T human CRC cells differing in their level of SST1 demethylation. Near-diploid LS174T cells underwent frequent genome-doubling events generating near-tetraploid clones with lower levels of SST1 methylation. In primary CRC, strong SST1 hypomethylation was significantly associated with global genomic hypomethylation and mutations in <i>TP53</i>. This work uncovers the association of the naturally occurring demethylation of the SST1 pericentromeric repeat with the onset of spontaneous tetraploidization in human CRC cells in culture and with <i>TP53</i> mutations in primary CRCs. Altogether, our findings provide further support for an oncogenic pathway linking somatic hypomethylation and genetic copy number alterations in a subset of human CRC.
format	article
author	Beatriz González Maria Navarro-Jiménez María José Alonso-De Gennaro Sanne Marcia Jansen Isabel Granada Manuel Perucho Sergio Alonso
author_facet	Beatriz González Maria Navarro-Jiménez María José Alonso-De Gennaro Sanne Marcia Jansen Isabel Granada Manuel Perucho Sergio Alonso
author_sort	Beatriz González
title	Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
title_short	Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
title_full	Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
title_fullStr	Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
title_full_unstemmed	Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
title_sort	somatic hypomethylation of pericentromeric sst1 repeats and tetraploidization in human colorectal cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1273cbe6e959447fbfd2d9c82c722e6c
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Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells

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