Publication: 17p13 (p53 locus), 5q21 (APC locus) and 9p21 (p16 locus) allelic deletions are frequently found in oral exfoliative cytology cells from smoker patients with non-small-cell lung cancer
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Date
2007
Authors
Sanz Ortega, J. ; Roig, F. ; Al-Mousa, M.M. ; Saez, M.C. ; Muñoz, A. ; Sanz Esponera, J. ; Callol, L.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Molecular cytogenetic and LOH analyses of
non-small cell lung cancer (NSCLC) have shown
frequent allelic deletions in a variety of chromosomes
where tumour suppressor genes are located. Allelic loss
at 9p21 (p16 locus), 17p13 (p53) and 5q21(APC) has
been frequently described in NSCLC and has also been
described in premalignant epithelial lesions of the
bronchus and normal bronchial cells. These findings
suggest that a tissue field of somatic genetic alterations
precedes the histopathological phenotypic changes of
carcinoma. Similar changes have been described in oral
and laryngeal epithelial tumours associated with smoke
exposure. We previously reported frequent LOH at 5q21,
9p21 and TP53 in tumor cells and peritumoral normal
bronchial cells from surgically resected NSCLC. We
now analyze 96 cases of normal oral exfoliative cytology
in which normal epithelial cells were obtained: 43 cases
from smoker patients with NSCLC diagnosis, 33 smoker
patients with no evidence of malignancy and 20 nonsmoker
patients with no evidence of tumour. All groups
had a similar age and sex distribution. PCR
amplification was performed utilising the specific
markers D5S346, D9S157 and TP53. In normal oral
mucosae cells from patients with NSCLC, we found that
21% of the informative cases showed LOH at any of the informative cases showed LOH at 5q21, 7.7% at 9p21
and 22.2% at TP53. Within the smoker risk group only
one case (4% of the informative cases) showed LOH at
TP53, while no LOH was found at 5q21 or 9p21. No
LOH was found in non-smokers. In conclusion, our
results show that a significant number of patients with NSCLC have LOH at TP53, 5q21 and 9p21 in normal
oral mucosae, while LOH at these loci is unusual in
similar cells obtained from patients with no evidence of
malignancy. Our study demonstrates that LOH studies
can detect smoker patients with a mutated genotype in
normal epithelial cells. Further prospective studies may
confirm whether LOH studies can detect patients with a
higher risk of NSCLC.
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