Allelic imbalance at the 5q14 locus is associated with decreased apoptotic rate in non-small cell lung carcinomas (NSCLCs). Possible synergistic effect with p53 gene alterations on apoptosis

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2000-06, Vol.28 (3), p.211-224
• Main Authors: Gorgoulis, V.G, Mariatos, G, Manolis, E.N, Zacharatos, P, Kotsinas, A, Liloglou, T, Vogiatzi, T, Tsagkaraki, A, Kokotas, S, Tsoli, E, Alchanatis, M, Sfikakis, P.P, Asimacopoulos, P.J, Field, J.K, Kittas, C
• Format: Article
• Language: English
• Subjects: 5q14; Aged; Apoptosis; Apoptosis - genetics; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cell Division; Chromosomes, Human, Pair 5 - genetics; DNA Primers - chemistry; DNA, Neoplasm - analysis; Female; Gene Frequency - genetics; Genes, p53 - genetics; Humans; In Situ Nick-End Labeling; Loss of Heterozygosity - genetics; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical sciences; Microsatellite Repeats - genetics; Middle Aged; Neoplasm Staging; NSCLC; p53; Ploidies; Ploidy; Pneumology; Prognosis; Proliferation; Survival Rate; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/S0169-5002(99)00137-3

Deletions in the 5q14 region have been described in a variety of neoplasms, such as testicular germ cell tumors, ovarian, gastric and lung cancer. The high frequency of allelic losses observed in this region implies the presence of putative tumor suppressor gene(s) (TSGs). In the present study, we investigated in a series of 56 non-small cell lung carcinomas (NSCLCs) the allelic imbalance (Alm) within the 5q14 region, employing the D5S644 marker, and its relationship with p53 abnormalities, the kinetic parameters [proliferation index (PI) and apoptotic index (AI)] and the ploidy status of the carcinomas. AI at D5S644 was found at a frequency of 51.2%. The rather high percentage of Alm in stage I tumors suggests an early involvement in NSCLC development. LOH at 5q14 was associated with decreased AR in lung tumors insinuating the presence of a putative TSG(s) ( P=0.008). Simultaneous alterations of both p53 and D5S644 locus were the most frequent pattern observed (37.5%). Cases demonstrating this profile also exhibited a marked decrease in AI ( P=0.001). These findings imply a synergistic mechanism of co-operation between different TSGs. However, proliferation activity was dependent only on p53 status, leading to the assumption that the putative TSG(s) present at 5q14 may probably be involved in normal apoptotic procedures. Further studies are needed to identify the candidate gene(s).