Chapter 20, Problem 30P

The website CBioPortal (http://www.cbioportal.org) is an exceptionally useful program for visualizing the cancer genes and genomes of tumors from thousands of patients with different kinds of cancer that have been analyzed by whole genome sequencing and in some cases, by RNA-Seq.

Go the the CBioPortal site and click All under Select Cancer Study and in Enter

Gene Set type PTEN, then hit Submit. On the page that is returned you will see how the coding region of the PTEN gene is altered in tumors investigated in the various studies. Hitting the tab Mutations will let you see the details of these mutations relative to the PTEN protein, while the tab Expression lets you see how the gene’s expression (in terms of cDNA reads) is altered in individual tumor samples.

a.	Is PTEN an oncogene or a tumor suppressor gene? What kinds of evidence lead you to this conclusion?
b.	What kinds of cancer are most likely to involve alterations of PTEN?
c.	How would you identify patients whose tumor cells are particularly likely to have a somatic mutation in the PTEN gene that is outside of the coding region but nonetheless contributes to cancer by affecting the gene’s regulation?
Now return to the CBioPortal home page. Again, select All under Select Cancer Study, but this time type ERBB2 under Enter Gene Set and then hit Submit.
d.	Is ERBB2 an oncogene or a tumor-suppressor gene? What kinds of evidence lead you to this conclusion?
e.	Are any kinds of listed mutations in the ERBB2 gene almost certainly passenger mutations as opposed to driver mutations? What does it mean to be a passenger mutation?
f.	If you were looking for regulatory mutations in the ERBB2 gene that are not in the coding sequence but that contribute to cancer, what attributes would you look for under the Expression tag?
g.	In comparing your results with the PTEN and ERBB2 genes, how informative are missense mutations in these genes with respect to possible contributions of such mutations to cancer phenotypes?