Dyskerin mediates both the modification of
uridine on ribosomal and small nuclear RNAs and the stabilization of the
telomerase RNA component (
TERC). In human
tumors dyskerin expression was found to be associated with both rRNA modification and
TERC levels. Moreover, dyskerin overexpression has been linked to unfavorable prognosis in a variety of
tumor types, however an explanation for the latter association is not available. To clarify this point, we analyzed the connection between dyskerin expression,
TERC levels and clinical outcome in two series of primary
lung cancers, differing for the presence of
TERC gene amplification, a genetic alteration inducing strong
TERC overexpression.
TERC levels were significantly higher in
tumors bearing
TERC gene amplification (P = 0.017). In addition, the well-established association between dyskerin expression and
TERC levels was observed only in the series without
TERC gene amplification (P = 0.003), while it was not present in
TERC amplified
tumors (P = 0.929). Similarly, the association between dyskerin expression and survival was found in cases not bearing
TERC gene amplification (P = 0.009) and was not observed in
TERC amplified
tumors (P = 0.584). These results indicate that the influence of dyskerin expression on
tumor clinical outcome is linked to its role on the maintenance of high levels of
TERC.