Oncogenes and tumor suppressor genes

Question 1

What distinguishes tumor suppressor genes from proto-oncogenes.

Answer 1

Tumor suppressor genes - loss of function increases cancer risk, both alleles must be lost for expression

Oncogenes - gain of function increases cancer risk, need damage to only 1 allele

Question 2

Explain Knudson’s two-hit hypothesis

Answer 2

Two “hits” or mutations to the designated allele are necessary to cause cancer. In the children with inherited retinoblastoma, the first mutation was inherited, and any second mutation would then lead to cancer. In non-inherited retinoblastoma, two “hits” had to take place before a tumor could develop, explaining the age difference.

Question 3

What is “loss of heterozygosity?”

Answer 3

An entire gene goes missing on an allele. This is relevant in cancer if the missing gene is a tumor suppressor gene. A person could then get cancer if the other allele for the gene is mutated. This is known as a “first hit” (loss) and “second hit” (mutation) as defined by Knudsen.

Question 4

Explain the consequences of mutations of tumor suppressor genes.

Answer 4

If tumor suppressor genes (eg: retinoblastoma or p53) are mutated for loss of function in both alleles, the cell will divide without regulation resulting in a tumor.

Question 5

Explain the consequences of mutations of oncogenes.

Answer 5

If oncogene genes (eg: der9:22 or HER2/NEU) are mutated on a single allele for a gain of function, cell growth will occur rapidly resulting in a tumor.