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24 Jun 2019

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Cancer Biology (Oncogenic Pathways)

The majority of malignant cells rely on dysregulation of a handful of oncogenes and their associated signaling pathways to support their abnormal proliferation and survival. The list below indicates the proteins that have become the ‘name sake’ for these key dysregulated pathways. Note that sometimes the protein listed is mutated and drives the pathway (ex. Ras), but other times it is rarely mutated (ex. Akt where PI3K and PTEN mutations predominate).

Working together in your groups, please create a portfolio of ‘profiles’ for the pathways shown below. For each pathway, include a map that links together the main proteins or molecules involved- ligands, receptors, transcription factors, etc... but always end with the ultimate effect on the cell! These pathway maps must be your own creation- do not copy other image files. For each protein or molecule you list in the map, please provide a ‘key’ that describes what it is, its specific function in the pathway, and detail where the most common pathogenic mutations occur in at least three proteins in the pathway (see below for details). Since these pathways can be extremely complex, you need not include more than three proteins or molecules at any one level in the pathway.

For information on the pathogenic mutations, use the COSMIC (catalogue of somatic muations in cancer) resource at http://cancer.sanger.ac.uk/cosmic . Enter the gene/protein name à click on the gene name in table below à under ‘Mutation Impact’ select Pathogenic à Apply. A bar graph depicting the various mutations will be shown, provide the number of confirmed mutations and the changes (DNA and amino acids) it causes at that site. For example, in the BRAF gene: 24,291 mutations have been confirmed that involve a T to A mutation at base 1799 which leads to a Valine (V) to Glutamic acid (E) amino acid substitution at position 600 (note this mutation constitutively activates the BRaf kinase).

Key Oncogenic Pathways to Profile:

Ras

Akt

Wnt

TGFB

Notch

Hedgehog

Grading will be based on aesthetic clarity, thoroughness and accuracy of the information.

Grading Rubric: 75 points total

Visuals: Aesthetic clarity 30 points

Pathways are well organized, easy to follow

activating and inhibitory relationships are readily apparent

Creative layout

Content: Thoroughness and Accuracy 30 points

All pathways completed

Essential level of detail in key

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Elin Hessel
Elin HesselLv2
26 Jun 2019

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