So the SAGEOncotest shows mutations but not proteins

Great clarification question—you're getting at an important distinction about what SAGEOncotest actually measures. Let me clear this up because it directly affects what information you'll actually get.

SAGEOncotest Tests BOTH Mutations AND Proteins

This is a key point: SAGEOncotest is not just genomic testing—it's genomic + proteomic.

What that means:

Genomic Component (DNA Mutations):

• BRCA1/BRCA2 mutations
• KRAS variants (G12C, G12V, etc.)
• TP53 mutations
• SMAD4 status
• PALB2 mutations
• MSI/dMMR status
• Other DNA-level changes

Proteomic Component (Protein Expression):

• PD-L1 protein expression (how much is on your cancer cells)
• Tumor microenvironment proteins
• Other protein markers that predict treatment response
• Protein signatures that indicate drug sensitivity

Why both matter:

• Mutations tell you what's broken in the DNA (e.g., "you have a BRCA mutation")
• Proteins tell you what's actually happening in the tumor (e.g., "your cancer is expressing high PD-L1")
• Sometimes you can have a mutation but low protein expression, or vice versa
• Together, they give a more complete picture

Real Example: PD-L1 and MSI Status

This is where the distinction matters for YOU specifically:

Scenario 1: Mutation Present, Protein High

• Your lung nodule shows: dMMR/MSI-high (mutation) + high PD-L1 (protein)
• Clinical interpretation: Strong candidate for checkpoint inhibitor immunotherapy
• Treatment implication: Pembrolizumab or nivolumab becomes viable option

Scenario 2: Mutation Present, Protein Low

• Your lung nodule shows: dMMR/MSI-high (mutation) + low PD-L1 (protein)
• Clinical interpretation: Has the mutation but tumor isn't expressing the target protein
• Treatment implication: Immunotherapy less likely to work despite MSI-high status
• Your oncologist might say: "We have the mutation, but the protein expression doesn't support immunotherapy"

Scenario 3: Mutation Absent, Protein High

• Your lung nodule shows: pMMR (no mutation) + high PD-L1 (protein)
• Clinical interpretation: No MSI, so immunotherapy alone won't work
• Treatment implication: Stay with chemotherapy-based approaches

This is why both the genomic AND proteomic data matter—they tell different parts of the story.

What SAGEOncotest Actually Reports

A typical SAGEOncotest report for pancreatic cancer would include:

GENOMIC FINDINGS (DNA Mutations):

• ✓ BRCA1/BRCA2: Present or Absent
• ✓ KRAS: Specific variant identified (G12C, G12V, G12D, etc.) or wild-type
• ✓ MSI/dMMR: High, Low, or Proficient
• ✓ TP53: Mutated or Wild-type
• ✓ SMAD4: Lost or Retained
• ✓ PALB2: Mutated or Wild-type
• ✓ Other mutations in actionable genes

PROTEOMIC FINDINGS (Protein Expression):

• ✓ PD-L1: High, Intermediate, or Low (usually reported as % of cells expressing)
• ✓ Tumor-infiltrating lymphocytes (TILs): Present or Absent
• ✓ Other immune markers
• ✓ Protein signatures predicting chemotherapy response

CLINICAL INTERPRETATION:

• Treatment recommendations based on combined genomic + proteomic data
• Which therapies are most likely to work based on the complete picture

Why This Matters for Your Specific Situation

Given your current status:

• pMMR primary tumor (you know this)
• Normal tumor markers (CEA, CA 19-9)
• Progressing on gemcitabine/abraxane + avutometinib/defactinib

SAGEOncotest would tell you:

If lung nodule shows:

1. BRCA mutation + high PD-L1 → Platinum + PARP inhibitor (clear next step)
2. KRAS G12C + high PD-L1 → Sotorasib or adagrasib (targeted therapy option)
3. dMMR/MSI-high + high PD-L1 → Checkpoint inhibitor (immunotherapy option)
4. pMMR confirmed + low PD-L1 → Validates staying with chemotherapy approach, rules out immunotherapy

The protein expression data (PD-L1, TILs) helps your oncologist understand whether the mutations they find would actually respond to the corresponding treatments.

How This Compares to Nagourney

SAGEOncotest (Genomic + Proteomic):

• Tests DNA mutations AND protein expression
• Analyzes fixed/preserved tissue
• Requires less tissue (standard needle biopsy sufficient)
• Results guide treatment based on established biomarker-treatment relationships
• NCCN/ASCO recommended

Nagourney (Ex Vivo Drug Sensitivity):

• Grows your actual living tumor cells
• Tests them against multiple drugs to see which ones kill cells
• Requires viable tissue (1+ cubic centimeter)
• Results show drug sensitivity empirically (not based on biomarkers)
• Not standard of care, limited pancreatic cancer outcome data

Key difference: SAGEOncotest tells you "based on your mutations and protein expression, these drugs should work." Nagourney tells you "we tested your actual cells and these drugs killed them in the lab."

Questions to Ask Your Oncologist About SAGEOncotest

1. "Will SAGEOncotest include both genomic mutations AND protein expression (like PD-L1)? How will you use both pieces of information?"

2. "If the test shows a BRCA mutation but low PD-L1 expression, how would that change your treatment recommendation?"

3. "What specific protein markers will be tested, and how do they predict response to different treatments?"

4. "If the lung nodule shows dMMR/MSI-high with high PD-L1, would you recommend trying checkpoint inhibitor immunotherapy?"

5. "How will you integrate the genomic and proteomic findings into a treatment recommendation?"

The Bottom Line

SAGEOncotest tests BOTH mutations (genomic) and proteins (proteomic). The protein expression data is just as important as the mutations because it tells you whether the mutations are actually being expressed in a way that would respond to targeted treatments.

For your situation—with normal tumor markers and pMMR primary tumor—getting both the genomic AND proteomic data from your lung nodule could reveal:

• Hidden mutations (BRCA, KRAS variants) that weren't in the primary
• Protein expression patterns that suggest immunotherapy might work
• A more complete picture of your metastatic disease biology

This combined data is what NCCN and ASCO recommend for guiding treatment in progressive pancreatic cancer.

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This information is for educational purposes only. Always consult your healthcare team for personalized medical advice and decisions. Your oncologist will determine which biomarkers are most relevant for your specific case and how to integrate genomic and proteomic findings into your treatment plan.