Oncogenes and tumor suppressor genes

In addition to epidemiological evidence, experimen-
tal evidence of the role of genes in lung cancer cau-
sation has been accumulating. First, it seems prob-
able that genetic changes are responsible for the
pathogenesis of most, if not all, human malignan-
cies [95]. In particular, lung carcinogenesis is the re-
sult of a series of genetic mutations that accumulate
progressively in the bronchial epithelium, first gen-
erating histologically identifiable premalignant le-
sions and finally resulting in an invasive carcinoma.
The premalignant genetic changes may occur many
years before the appearance of invasive carcinoma.
Cytogenetic and molecular studies have shown
that mutations in protooncogenes and tumor sup-
pressor genes (TSGs) are critical in themultistep de-
velopment and progression of lung tumors. Allele
loss analyses have implicated the presence of other
tumor suppressor genes involved in lung tumorige-
nesis. These studies revealed frequent occurrences
of chromosomal deletions including regions of 3p,
5q, 8p, 9p, 9q, 11p, 11q, and 17q. These studies are
outside the scope of this chapter (see e.g. [96–98]
for reviews).