Four classes of normal regulatory genes are the principal targets of genetic damage:

 the growth-promoting protooncogenes
 the growth-inhibiting tumor suppressor genes
 genes that regulate programmed cell death (apoptosis)
 genes involved in DNA repair

Mutant alleles of proto-oncogenes are considered dominant because they transform cells despite the presence of a normal counterpart.

In contrast, both normal alleles of the tumor suppressor genes must be damaged for transformation to occur, so this family of genes is sometimes referred to as recessive oncogenes. However, there are exceptions to this rule, and some tumor suppressor genes lose their suppressor activity when a single allele is lost or inactivated. This loss of function of a recessive gene caused by damage of a single allele is called haploinsufficiency.

Genes that regulate apoptosis may be dominant, as are protooncogenes, or they may behave as tumor suppressor genes.

Methodology for cloning of cancer genes

 identification of viral oncogenes
 identification of genes associated with recurrent chromosomal aberrations
 screens for genes capable of the transformation of cells in culture
 whole genome, high-throughput screens
 murine leukemia virus-based mutagenesis
 Sleeping Beauty-based mutagenesis
 RNA interference
 exon re-sequencing
 high-resolution methods for detecting chromosomal amplifications and deletions

References

 Collier LS, Largaespada DA. Transforming science: cancer gene identification. Curr Opin Genet Dev. 2006 Feb;16(1):23-9. PMID: #16326095#

 Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004 Aug;10(8):789-99. PMID: #15286780#

 Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR. A census of human cancer genes. Nat Rev Cancer. 2004 Mar;4(3):177-83. PMID: #14993899#