E-Locus - Institutional Repository of the University of Crete - Μελέτη του ρόλου των μεταλλαγών στα γονίδια p14ARF, p15INK4b και p16INK4a και της γενωμικής αστάθειας στην ακτινική υπερκεράτωση

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Identifier

000348350

Title

Μελέτη του ρόλου των μεταλλαγών στα γονίδια p14ARF, p15INK4b και p16INK4a και της γενωμικής αστάθειας στην ακτινική υπερκεράτωση

Author

Κανέλλου, Πέγκυ

Thesis advisor

Σπαντίδος, Δημήτριος

Reviewer

Ζώρας, Οδυσσέας
Χρυσός, Ε.
Σαμώνης, Γ.
Κραμποβίτης, Η.
Σουρβίνος, Γ.
Κρασαγάκη, Κ.

Abstract

Actinic keratosis (AK) is a well-established pre-cancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). We investigated the involvement of the CDKN2A, CDKN2B and p53 genes in AK and in the progression of AK to SCC. Mutational analysis on exons 1a, 1b and 2 of the CDKN2A locus and exon 1 of the CDKN2B locus as well as allelic imbalance was performed in 26 AK specimens. Expression levels of the genes p14ARF, p15INK4b, p16INK4a and p53 were examined in 16 AKs and 12 SCCs by real-time RT-PCR. A previously-described polymorphism of p16INK4a (Ala148Thr) was detected at an allelic frequency of 12%. Six samples carried novel mutations at codon 71 of the CDKN2A locus and one sample presented an additional mutation at codon 65. Two AK samples carried a notpreviously described non-UV type missense mutation at codon 184 (Val184Glu) of exon 1b in the p14ARF gene. Regarding the CDKN2B locus a new mutation at codon 50 (Ala50Thr) and another at codon 24 (Arg24Arg), were detected. Microsatellite instability (MSI) was found in at 15% of AKs in at least one marker, indicating that genetic instability has some implication in the development of AK. Down-regulation of p16INK4a and p53 mRNA levels was noted in SCC compared to AK. TSGs expression levels in sun-exposed morphologically normal-appearing skin, suggests that abnormal growth stimuli might exist in these tissues as well. Furthermore, we suggest a possible role of p15INK4b, independently from the intracellular pathway mediated by p16INK4a, and of p14ARF in AK development, as well as in the progression of AK to SCC. The deregulation of the expression profiles of the CDKN2A, CDKN2B and p53 genes may, independently of mutations and LOH at 9p21, play a significant role in AK and progression of AK to SCC.

Physical description

xiii, 175 σ. : πιν. ; 30 εκ.

Language

Greek

Subject

Keratosis

Oncogenes

Skin Neoplasms

Νεοπλάσματα δέρματος

Υπερκεράτωση

Issue date

2008-04-03