P53 GENETIC ABNORMALITIES AND MYC ACTIVATION IN HUMAN LUNG-CARCINOMA

p53 mutations and myc gene amplification and expression were studied i n 119 lung carcinomas of all histological types. A mutant p53 immunoph enotype was previously found in 47% of these tumors by immunohistochem ical analysis. Seven cases exhibited p53 genomic rearrangements on Sou thern blots. Elevated levels of p53 transcript were found in 12 carcin omas (10%) and decreased levels in 27 carcinomas (23%) on Northern blo ts. In most of the cases, low levels of transcript were associated wit h negative immunostaining, whereas elevated levels of mRNA were relate d to positive immunostaining (mutant immunophenotype). p53 RT/PCR anal ysis in 10 tumors with absence of transcript on Northern blots reveale d only weak or absent expression of normal and/or altered size transcr ipts. These abnormal transcripts showed deletions, insertions or splic ing abnormalities. Taken together, p53 abnormalities were found in 66% of lung carcinomas [52% of neuroendocrine (NE) carcinomas and 75% of NSCLC]-c-myc was found to be activated in 24% (10/42) of these NE and in 48% (33/69) of these NSCLC carcinomas using Southern- and Northern- blot techniques. In addition, L- and N-myc genes were also activated i n 26% (10/42) of NE carcinomas. No correlation was found between p53 m utations and myc activation in SCLC or in nsclc, but their association was significantly more frequent in NSCLC than in SCLC. These results indicate that the p53-positive immunophenotype uncovers the occurrence of p53 point mutations in lung cancer and that p53 and c-myc gene alt erations are important but represent independent occurrences in the de velopment of lung tumors. (C) 1994 Wiley-Liss, Inc.