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 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.


CONCLUSIONS
These data suggest that centromeric instability is associated with genomic DNA hypomethylation only when occurring at specific DNA repeat sequences.
Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Spain.
Jorge García
JG
Martínez
Jhudit
J
Pérez-Escuredo
Patricia
P
Castro-Santos
César Alvarez
CA
Marcos
José Luis Llorente
JL
Pendás
Mario F
MF
Fraga
Mario A
MA
Hermsen
D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002503:Centromere / Q000235:genetics; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA