Zoo 317 Heredity, Evolution and Society
|Lecture 27||Cummings 14: pp 330-338|
II. Inherited risk of cancer.
III. Tumor suppressor genes.
p. 349, Summary, No. 1: Misleading. Cancer per se is very rarely present at birth. However, there are a number of genotypes for which the risk of eventual development of cancer is 100%, provided something else doesn't get you first.
I. Tumors are abnormal growth of tissue. Most involve somatic cells.
2. They can invade other tissues.
2. Some benign tumors can evolve into malignant tumors, a process sometimes referred to as transformation.
2. They are not subject to the normal regulation or restraints on growth.
3. Over time, cancer cells evolve from a slow-growing form to more aggressive growth. This happens through a series of stepwise changes, each representing a new clonal population.
2. Certain chemicals.
3. Certain rare viruses, such as Rous sarcoma virus in chickens and mouse mammary tumor virus.
4. In some families, heredity is important.
B. Cancer clusters in some families at a much higher rate. In some of these, simple Mendelian dominant inheritance is obvious. Examples include:
2. Retinoblastoma is a malignant tumor that develops from embryonic cells in the retina (retinoblasts) in young children. After several years of age, retinoblasts are no longer present and the risk of developing new retinoblastomas virtually disappears. In many instances, the risk of retinoblastoma is transmitted as an autosomal dominant trait, although penetrance is less than 100%. The RB locus is at 13q14. Nonfamilial (isolated) cases of retinoblastoma also occur.
3. Two major breast cancer genes have now been isolated. BRCA1 on chromosome 17 carries a high risk of breast and ovarian cancer. BRCA2 on chromosome 13 carries a high risk of breast (but not ovarian) cancer. The risk of breast cancer in males is also increased with mutations in BRCA2.
B. In retinoblastoma and in most other dominantly inherited cancers, the presence of one normal allele is sufficient to suppress development of cancer. This suppression is lost when both alleles become nonfunctional. Therefore, when the locus is functioning normally, tumors do not develop.
C. In general, the function of tumor suppressor genes is to regulate the cell cycle. The product of the RB locus, a protein designated RB, regulates progression from G1 into S. When RB is in its unphosphorylated form, progression does not occur. When RB is inactivated by phosphorylation in a normal cell, the transition from G1 to S occurs and the cell eventually divides. The state of phosphorylation of RB is controlled by a complex network of other regulatory proteins. If functional RB is missing because of mutation, cells divide continuously.
|clonal||multiple polyposis of the colon||retinoblastoma|
|tumor suppressor gene|| || |