Expression of aphidicolin-induced fragile sites and their
relationship between genetic susceptibility in breast cancer, ovarian cancer,
and non-small-cell lung cancer patients.
Dhillon VS, Husain SA, Ray GN.
Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital,
Camperdown, Australia.
Fragile sites are nonrandomly located gaps and/or breaks and their expres-sion
can be induced by specific culture conditions. There are many reports in the
literature that indicate that these sites can act as factors that predispose to
specific chromosome aberrations and other complex rearrangement in the
chromosome and their association with cancers. In the present study, the
expression of the fragile sites induced by aphidicolin was evaluated on
prometaphase chromosomes from peripheral blood lymphocytes of 55 patients with
breast cancer patients belonging to different stages of the cancer, 25 patients
with epithelial ovarian cancer, and 13 with non-small-cell lung cancer, 100 of
their first-degree clinically healthy female relatives, and 100 normal
age-matched healthy persons without a familial history of cancer. The frequency
of expression of the fragile sites in cancer patients and their first-degree
relatives was found to be statistically significant (P<0.05) than those of the
controls. In different stages of breast cancer patients, 6q26 is the
best-defined fragile site whereas 13q13 is confined to stage II and stage III
patients only. The chromosomal aberration rate/cell in breast cancer patients
was found to be 0.29+/-0.13, in epithelial ovarian cancer patients 0.38+/-0.14,
and in non-small-cell lung cancer 0.29+/-0.11 as compared to 0.07+/-0.03 in
controls, and was found to be statistically significant. Therefore, our results
indicate that these fragile sites may be the unstable sites in the genome and,
hence, can be used as suitable and reliable markers for genetic predisposition
to breast cancer, epithelial ovarian cancer, and in non-small-cell lung cancer.
Teratogenesis Carcinog. Mutagen. Suppl. 1:35-45, 2003. Copyright 2003 Wiley-Liss,
Inc.
