Variant Calling & Mutational Signature Lab

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Assemble your responses (QUESTIONS 1-8) into one PDF ❗ ❗

QUESTION 1

1. Go to the Mutational Signatures siteLinks to an external site. and click on “SigProfilerAssignment” → “Get started” → “I acknowledge…”
2. Download the file filtered_colo829.vcfDownload filtered_colo829.vcf and rename it to “lastname_firstname_colo829.vcf”
3. Upload the renamed VCF file with the following parameters:
   input = “Mutation calling file”,
   1. Mutation calling file format = “VCF”,
   2. reference = “hg19/GRCh37”,
   3. variant class = “SBS”,
   4. reference mutational signatures = “COSMIC v3.4”,
   5. type of study = “Whole-genome”.

Attach a screenshot showing the file name and sample recognized on the COSMIC upload page.

QUESTION 2

Click on the “Samples reconstruction” tab to show the mutation mutational spectrum.

• Download the PNG image.
• Insert the PNG into your document.

QUESTION 3

Copy the signature contributions shown in the spectrum. Report the signatures detected and their proportional contributions exactly as shown (e.g., “SBS4 = 35.74%”).

QUESTION 4

For each detected signature, answer in ≤ 100 words:

1. Mutational process/etiology (what causes it?)
2. Typical base-substitution pattern (e.g., C>T at CpG; CC>TT)
3. Why it is expected / unexpected in melanoma

QUESTION 5

Concept check – Tumour-Suppressor Genes vs. Oncogenes

Explain, in your own words (≤ 150 words total):

1. what defines a tumour-suppressor gene (TSG)
2. what defines an oncogene
3. the key difference in the kinds of mutations that activate each class during cancer development

QUESTION 6

Using the Cancer Gene CensusLinks to an external site. (or NCBI Gene / COSMIC Gene Summary), place each mutated gene below into one of the three categories. Use the table format provided. A single gene may be marked “U” (dual/uncertain) if credible sources disagree.

ATR • BIRC6 • BRAF • CSMD3 • CTNNA2 • DCC • ERBB3 • ERBB4 • GLI1 • MET • MUC16 • PDGFRA • SF3B1 • TNC • TP63

Cancer Gene Census

Gene	O = Oncogene	T = Tumour-suppressor	U = Uncertain

QUESTION 7

Choose four genes from Q6 (at least one oncogene and one TSG). For each selected gene, provide 2–3 concise bullet points that address:

• Type of mutation observed in COLO-829 and its impact on the protein (gain- or loss-of-function, splice defect, etc.).
• How that altered protein activity contributes to melanoma growth, survival, or metastasis.
• Connection (if any) to UV-induced DNA damage pathways or selection pressures.

QUESTION 8

Insert a brief concluding paragraph (≤ 75 words) summarizing how the dominant UV signatures you observed align with the driver mutations identified in Q7.