B lymphocytes produce antibodies. IgH encodes one class of antibody polypeptides. IgH enhancer causes high levels of txn in B lymphocytes. IgH enhancer causes increased txn of bcl2 gene. Bcl2 inhibits apoptosis, allowing cells to survive longer and accumulate mutations. Found in several kinds of B lymphocyte cancers (e.g., follicular lymphoma)

Tumor Suppressor Genes Two examples Retinoblastoma (Rb): Inhibits txn of E2F target genes. In Rb-/ Rb- cells, E2F always activates txn of target genes. p53: Checkpoint: Detects damaged DNA. Activates p21. p21 inhibits phosphorylation of Rb by cdk2-cyclin A. p53-/ p53- cells don’t stop dividing when DNA is damaged. Accumulate mutations & other genomic abnormalities. TF: Activates txn of Fas receptor gene. In p53-/ p53- cells, expression of Fas receptor decreases. Inhibits damaged cells from entering apoptosis pathway.

Extracellular Regulation of Apoptosis Fas Ligand Positive Regulation Activated Fas receptor activates Apaf

Inherited risk for certain cancers Retinoblastoma

10-12 10-6 10-6 Usually, patients develop a single tumor in one eye due, in part, to very rare mutations in both copies of Rb gene.

Due to inheritance of a mutant Rb allele. (Familial) 10-6 In some families, multiple children develop Retinoblastoma, and often in both eyes. Due to inheritance of a mutant Rb allele.

Inherited risks for other cancers also due to inheritance of mutant alleles of tumor-suppressor genes Examples: Breast Cancer: 75% of familial breast cancers associated with inheritance of mutant allele of BRCA1 or BRCA2. Xeroderma Pigmentosum: Inheritance of mutant allele of gene that codes for DNA repair protein.

Summary of mutations that contribute to the evolution of tumors Oncogenes Tumor Suppressor Genes