| Abstract: | Chromosome instability, a genetic condition inducing a
large number of genetic and chromosome alterations, is
a shared feature of most cancers. Using a molecular
approach, recent studies on the telomere–telomerase
complex in the peripheral blood of patients with familial
papillary thyroid cancer (FPTC) have shown the
presence of short telomeres and hTERT gene amplification
and expression. To study the phenomenon at the
chromosomal level, we investigated the presence of
chromosome breakage, telomeric association (TA) and
telomeric fusion (TF) in phytohemagglutinin-Mstimulated
lymphocytes from FPTC patients, unaffected
family members (UFM) and healthy subjects (HS). T
lymphocyte cultures were obtained from peripheral
blood of 13 FPTC patients, 6 UFM and 10 HS.
Spontaneous chromosomal instability was evaluated
by scoring for TA and chromosomal breakage (gaps,
breaks, centric fissions, acrocentric fragments, rings,
min/dmin) Giemsa-stained metaphases (200/sample),
whereas TF was studied on PNA-telomeric probe (QFISH)
hybridized metaphases (50/sample). Q-FISH also allowed measuring the telomere length. Duplication/
amplification of the hTERT gene was investigated by
fluorescence in situ hybridization (FISH). FPTC
patients displayed increased spontaneous chromosome
instability, both with conventional (p=0.045) and
molecular (p=0.026) cytogenetic analysis as compared
with the other categories. FPTC patients showed a
higher frequency of telomeric association than UFM
(p=0.00034). Q-FISH analysis revealed that FPTC
patients have shorter telomeres (dark telomeres, p=
0.015) as compared with other groups and have a
significantly increased number of non-acrocentric (p=
0.039) and acrocentric fusions (p=0.04) and acentric
fragments with double telomeric signal (p=0.005) as
compared with HS. A few cells from FPTC patients
showed three copies of the hTERT gene as compared
with UFM and HS cells; however, the result was not
statistically significant. Our data confirm the presence
of short telomeres in cells from FPTC patients and
demonstrate that this phenomenon favours elevated
chromosome instability, including telomeric fusion. |
