Hypomethylation of LINE-1, and not centromeric SAT-α, is associated with centromeric instability in head and neck squamous cell carcinoma

Background Head and neck squamous cell carcinoma (HNSCC) is a tumour type that generally carries very complex chromosomal aberrations. An interesting feature is the elevated occurrence (58 %) of whole arm translocations and isochromosomes, resulting from breakage and illegitimate recombination in ce...

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Published in:Cellular oncology (Dordrecht) 2012-08, Vol.35 (4), p.259-267
Main Authors: Martínez, Jorge García, Pérez-Escuredo, Jhudit, Castro-Santos, Patricia, Marcos, César Álvarez, Pendás, José Luis Llorente, Fraga, Mario F., Hermsen, Mario A.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Line, Tumor
Centromere - genetics
Chromosome Aberrations
Comparative Genomic Hybridization
DNA Methylation
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - pathology
Humans
Karyotyping
Long Interspersed Nucleotide Elements - genetics
Male
Middle Aged
Oncology
Original Paper
Pathology
Repetitive Sequences, Nucleic Acid - genetics
Sequence Analysis, DNA
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Summary:Background Head and neck squamous cell carcinoma (HNSCC) is a tumour type that generally carries very complex chromosomal aberrations. An interesting feature is the elevated occurrence (58 %) of whole arm translocations and isochromosomes, resulting from breakage and illegitimate recombination in centromeric or pericentromeric regions. We hypothesized that alterations in DNA methylation may play a role in the breakage of centromeric repeat sequences in these tumours. Methods We studied the DNA methylation status of global repeats (LINE-1), subtelomeric repeats (D4Z4) and centromeric repeats (SAT-α) in relation to centromeric instability in a series of HNSCC cancer cell lines and primary tumours. We analysed the methylation status by pyrosequencing and the chromosomal aberrations by microarray CGH. Results We found a significant association between centromeric instability and hypomethylation of LINE-1, but not D4Z4 and SAT-α. Conclusion These data suggest that centromeric instability is associated with genomic DNA hypomethylation only when occurring at specific DNA repeat sequences.
ISSN:2211-3428
2211-3436
DOI:10.1007/s13402-012-0085-5