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

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 prese nce of putative tumor suppressor gene(s) (TSGs). In the present study, we i nvestigated in a series of 56 non-small cell lung carcinomas (NSCLCs) the a llelic imbalance (Alm) within the 5q14 region, employing the D5S644 marker, and its relationship with p53 abnormalities, the kinetic parameters [proli feration 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 i nsinuating the presence of a putative TSG(s) (P = 0.008). Simultaneous alte rations of both p53 and D5S644 locus were the most frequent pattern observe d (37.5%). Cases demonstrating this profile also exhibited a marked decreas e in AI (P = 0.001). These findings imply a synergistic mechanism of co-ope ration between different TSGs. However, proliferation activity was dependen t only on p53 status, leading to the assumption that the putative TSG(s) pr esent at 5q14 may probably be involved in normal apoptotic procedures. Furt her studies are needed to identify the candidate gene(s). (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.