The typical chromosomal aberrations, present in SCLC and NSCLC cells, include aneuploidy, chromosomal trans­locations, and amplifications.

      Aneuploidy. Aneuploidy is an abnormal number of chromosomes within the cell nucleus. At the cytogenetic level it distinguishes between cancer cells and pre-malig­nant lesions from normal lung epithelium. While pre-inva­sive tissues tend to be diploid with only a few aberrations (gain in chromosome 7, loss in 3p and 9p), invasive and metastatic tumors are generally aneuploid. Aneuploidy of pre-invasive tissue has been reported only when the tumor was aneuploid, supporting the theory of field canceriza­tion. A single aneuploidy was detected in squamous dys­plasia [1] and in high risk smokers [2]. In invasive lung carcinoma it includes a number of chromosomes. Thus, an accumulation of chromosomal imbalances was detected during carcinogenesis as a cause of progression from nor­mal through pre-invasive to invasive tumors.

      New technologies such as spectral karyotyping (SKY), fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH), provide useful information about the chromosomal abnormalities in lung cancer. The use of FISH for assessment of aneuploidies in lung cancer, has established that the most frequent gains are seen in chromosome 7 (82%) [3].

      Specific Chromosomal Translocation. A specific translocation in NSCLC is t(15; 19) which results in the over expression of Notch3 [4]. Karyotype analysis per­formed on 2429 primary tumor specimens, demonstrated high frequency of this translocation t(15; 19) (q11; p13). In a transgenic mouse model, Notch3 over expression keeps cells in an undifferentiated state [5].This identifies Notch3 as a potential oncogene in lung cancer.

      Amplification Regions. Amplification structures are small acentric chromosomal fragments, called double min­utes, or homogeneously staining regions (HSR). Results from CGH studies show common regions of amplification on 1q, 3q 5p, 8q, 11q 12p 17q, 20q in NSCLC [6].

      From Amplification Regions to Target Genes. Am­plification of 3q was the most prevalent in squamous cell carcinoma, being present in 75-94% of the tumors [7]. A common amplicon at 3q26-q28 that codes the catalytic subunit of phosphatidylinositol-3-kinase (PIK3CA) was identified by array CGH [8]. It controls a critical pathway that is involved in cell survival and cell division. This amplicon also contains a p53 homolog p63, which is also a commonly amplified gene in squamous cell carcinoma [9]. The p63 regulates cell growth and differentiation. An increased copy number for p63 was detected by FISH and immunohistochemistry on tissue microarray of a large collection of NCSLC.