Somatic hypomethylation of pericentromeric sst1 repeats and tetraploidization in human colorectal cancer cells
González Fernández, Beatriz (Institut Germans Trias i Pujol)
Navarro Jiménez, Maria (Institut Germans Trias i Pujol)
Alonso De Gennaro, María José (Institut Germans Trias i Pujol)
Jansen, Sanne Marcia (Institut Germans Trias i Pujol)
Granada, Isabel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Perucho, Manuel (Sanford Burnham Prebys Medical Discovery Institute (SBP))
Alonso, Sergio (Institut Germans Trias i Pujol)

Fecha:	2021
Resumen:	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 TP53. 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 TP53 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.
Ayudas:	Instituto de Salud Carlos III FIS PI18/01484
Nota:	Altres ajuts: This work has been supported by a grant to MP and SA from the Instituto de Salud Carlos III (FIS PI18/01484), Spanish Ministry of Science, Innovation and Universities, FEDER.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Genomic DNA hypomethylation ; Colorectal cancer ; Tetraploidization ; Chromosome instability ; Repetitive elements ; Polyploidy
Publicado en:	Cancers, Vol. 13 Núm. 21 (11-1 2021) , p. 5353, ISSN 2072-6694

DOI: 10.3390/cancers13215353
PMID: 34771515

22 p, 2.7 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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