Although some oncogenes and tumor suppressor genes have a restricted distribution that hints at likely tumor locations, many of the genes are widespread and even ubiquitous. It is presently unclear, therefore, why certain types of cancer are linked to particular mutated genes, but there are a number of strongly correlated cases.
Cancers are classified by the tissue type in which the tumors first arise. Thus, carcinomas, which are the most common type (~85% of human cancers), come from epithelial cells arising from either the embryonic ectoderm (skin and nerve cells) or endoderm (gut lining). Leukemias (~4%) arise from white blood cells. Lymphomas (~5%) reflect aberrant growth of lymphocytes in spleen or lymph nodes. Sarcomas (~2%) arise from connective tissue of mesodermal origin, such as bone cancers.
Retinoblastoma is a cancer of the eye that usually strikes at a relatively young age. It has been linked to the RB gene, which encodes a repressor of E2F, a transcription factor that would normally turn on genes needed for S phase progression. Only 10% of individuals who inherit the RB loss-of-function mutation escape the development of the cancer. It also turns out that people with the RB mutation have a higher incidence of developing other tumors as well, although generally later in life. Perhaps the higher rate of damage to retinal cells (due to light exposure) leads to greater susceptibility.
Breast cancer is another disease that has strong links to mutations in certain genes. Loss of function mutations to the BRCA1 gene encoding a DNA repair protein lead to a five-fold higher risk of developing breast cancer in a woman’s lifetime. Although mutations to other tumor suppressors (including p53, PTEN, CHEK2, ATM) most hereditary breast cancers have a link to BRCA1 or BRCA2 mutation. On the oncogene side, breast cancer tumors consistently show expression of CYCD1 (a cyclin) mutations, and depending on the type of tumor, HER2/Neu may be linked as well.
Lung cancers are among the most common - the second highest in men (prostate is higher) and women (breast is higher) alike, and make up approximately 1 in 3 cancer deaths annually. Several oncogenes of the myc family: N-myc, L-myc, and c-myc, as well as H-ras have been linked to various lung cancers. Loss of p53 and RB are also associated with the development of lung cancers, and perhaps not coincidentally, tobacco smoking is associated with p53 mutations. Interestingly, despite being so common, so far, there have been no particular oncogenes associated with prostate cancer, nor any hint of prostate-specific tumor suppressor susceptibilities.