biology college question

Question

In Chronic Myelogenous Leukemia (CML; cancer of blood precursor cells), patients have a translocation between chromosomes 9 and 22 (meaning that these two chromosomes swap part of their chromosome arms). On one of the fused chromosomes, part of a gene called BCR becomes fused to a gene called ABL, resulting in a new protein, "BCR-Abl." Only one copy of this fused gene is present in patients. Putting one copy of the fused human ORF (behind a bone marrow-specific promoter) into mice causes leukemia in the mice and these leukemia cells only have one copy of the BCR-ABL gene.

a. How many alleles must be mutant to cause CML?

b. Is the mutant BCR-ABL allele dominant or recessive to the wildtype ABL allele?

c. How many RN alleles must be mutant to cause retinoblastoma?

d. Is the mutant RB allele dominant or recessive to the wildtype RB allele?

Answer 1

A really great explanation of this phenomenon -- and of how it was discovered -- is given in _The Emporer of All Maladies_ by Siddhartha Mukherjee. If you wish to dive deep into this subject, I recommend this book!

But in short, some cancers require only one change because that change creates a "stuck" cell cycle promoter. The change can be described as from proto-oncogene (a wild-type, harmless cell cycle promoter that can be turned on/off by the cell) to oncogene (an altered cell cycle promotor that cannot be shut off by the cell).

Other cancers, such as retinoblastoma, are caused by the change of a repressor gene from wild-type to altered. In these cases, BOTH copies of the suppressor gene must be changed to cause cancer; even one still intact can suppress the unregulated growth of the tissue.

In this sense, an oncogene is "dominant" because one copy will cause uncontrolled cell proliferation; but a damaged repressor gene is "recessive" because it does not cause cancer if only one of the native pair has been "mutated."