Jose is a 32-year old landscaper living in Pheonix, Arizona. He and his 64-year-old father, Ray, were both diagnosed with metastatic melanoma within two months of one another. Both had their tumors biopsied to look for potential targets for targeted therapy. The BRAF proto-oncogene from each of their tumors was sequenced. Their cancer cells were analyzed for expression of PD-L1. The data are shown in the table below.
| BRAF gene sequence (corresponding to amino acids 598-602; note that the DNA groups shown below corresponds to mRNA codons) | PD-L1 expression | |
| José | CGA TGT CTC TTT AGA | No |
| Ray | CGA TGT CAC TTT AGA | Yes |
[a] Transcribe and translate the BRAF gene sequences from Jose and Ray’s tumors. What amino acid is at position 600 in each? Use the dictionary of the genetic code.
[b] Zelboraf is a drug that stops division of metastatic melanomas by blocking the activity of a mutant (oncogenic) BRAF protein that has a glutamic acid at position 600 (the proto-oncogene has a valine at position 600). Keytruda is an antibody drug that blocks the interaction between PD-L1 on cancer cells and its binding partner (PD-1) on immune cells. Given their individual tumors, what treatments are best for Jose and Ray? Consider both targeted and traditional therapies and justify your answer.
[c] From the information presented, do you think this is more likely to be a case of inherited cancer or two cancers that just happened to occur in these two family members? Explain your answer and consider other risk factors that may be involved for Jose and Ray.
