Genomic characterization of early-stage asymptomatic lung cancers

Background: CT screening of lung cancer allows the detection of very small tumors. The objective of our study was to verify whether a selected population of initial asymptomatic lung cancers show genetic abnormalities able to mark the early events of lung carcinogenesis. Methods: A pilot study was performed for the standardization of the technique, enrolling heavy smokers with asymptomatic early stage lung cancers non-screening detected. Since 2004, a low dose CT screening study enrolled 5201 asymptomatic heavy smokers volunteers. Tissue samples were collected from patients of these two groups who underwent surgical resection in our institute and short-term cultures were started from tumoral tissues. Cultures were suitably treated for the analysis of metaphase spreads. Samples were classified according to the normal (N) or aneuploid (A) karyotype. N samples were further analyzed by the Affymetrix HuSNP 50K technology. Results: 101 tumor samples were analyzed (33 collected during a pilot project and 78 as part of the screening program). Metaphase spreads were obtained in 70% (71/101) of the selected samples: 77% (55/71) showed an aneuploid karyotype, while 20% (14/71) resulted as normal, 3% (2/71) were uncharacterized. The subgroup of tumors with p-stage IA showed aneuploidy in 70% (24/34) of cases with a mean size of 15 mm. A correlation between tumor size and chromosome number was shown, having small size tumors a higher probability to show a normal karyotype. 8/14 of the N samples were found suitable for SNPs analysis. Subtle genomic alterations were found in 4 of the analyzed patients, the remaining 4 lacking to date of an evidence for the presence of chromosomal aberrations throughout the genome. A common region of amplification was identified at 8p11 in 2 samples and is currently under investigation. Conclusions: i) The majority of screening detected tumors presented aneuploidy despite very initial stage. ii) A correlation between tumor size and ploidy status exists in early lung cancers. ii) Genomic scanning is able to detect subtle region of chromosomal alterations in early lung cancer patients.