mmr_reference.svg

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<title>MMR in cancer — a reference</title>
<desc>MMR (the cause) at top; high MMR activity gives MSS, low gives MSI-H; each state then drives the immune response (MSS cold, MSI-H hot). Plus an MSI-H/MSS readout and what gene expression can detect.</desc>
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<text x="30" y="22" font-size="13" font-weight="700" fill="#23303A">1 · The biology  <tspan font-weight="400" fill="#6E7F8C" font-size="11">(top → bottom = cause → effect)</tspan></text>

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<text x="380" y="62" text-anchor="middle" font-size="12.5" font-weight="700" fill="#23303A">MMR — the spell-checker</text>
<text x="380" y="82" text-anchor="middle" font-size="11" fill="#6E7F8C">MLH1 · MSH2 · MSH6 · PMS2</text>

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<text x="190" y="214" text-anchor="middle" font-size="12.5" font-weight="700" fill="#2C5563">MSS — spell-checker WORKING</text>
<text x="190" y="234" text-anchor="middle" font-size="11" fill="#5A6670">stable DNA · low TMB</text>

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<text x="570" y="214" text-anchor="middle" font-size="12.5" font-weight="700" fill="#8A4E20">MSI-H — BROKEN (dMMR)</text>
<text x="570" y="233" text-anchor="middle" font-size="11" fill="#8A4E20">unstable DNA · HIGH TMB</text>
<text x="570" y="251" text-anchor="middle" font-size="11" font-weight="700" fill="#8A4E20">→ responds to immunotherapy</text>

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<text x="380" y="384" text-anchor="middle" font-size="12.5" font-weight="700" fill="#23303A">Immune system</text>
<text x="380" y="404" text-anchor="middle" font-size="11" fill="#6E7F8C">CD8A · GZMA · PRF1 (T-cell attack)</text>

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<text x="250" y="148" font-size="11" font-weight="700" fill="#2C5563">MMR HIGH</text>
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<text x="500" y="148" font-size="11" font-weight="700" fill="#8A4E20">MMR LOW</text>

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<text x="232" y="312" font-size="11" font-weight="700" fill="#6E7F8C">immune LOW</text>
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<text x="492" y="318" font-size="11" font-weight="700" fill="#8A4E20">immune HIGH</text>

<text x="30" y="456" font-size="13" font-weight="700" fill="#23303A">2 · MSI-H vs MSS readout</text>
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<text x="300" y="478" text-anchor="middle" font-weight="700" fill="#8A4E20">MSI-H (broken)</text>
<text x="580" y="478" text-anchor="middle" font-weight="700" fill="#6E7F8C">MSS (working)</text>
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<text x="40" y="506">MMR activity</text><text x="300" y="506" text-anchor="middle" fill="#8A4E20">LOW</text><text x="580" y="506" text-anchor="middle" fill="#6E7F8C">normal / HIGH</text>
<text x="40" y="530">TMB (mutation count)</text><text x="300" y="530" text-anchor="middle" font-weight="700" fill="#8A4E20">↑ HIGH</text><text x="580" y="530" text-anchor="middle" fill="#6E7F8C">↓ LOW</text>
<text x="40" y="554">immune attack (CD8A…)</text><text x="300" y="554" text-anchor="middle" font-weight="700" fill="#8A4E20">↑ hot</text><text x="580" y="554" text-anchor="middle" fill="#6E7F8C">cold</text>
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<text x="40" y="584" font-weight="700">immunotherapy</text><text x="300" y="584" text-anchor="middle" font-weight="700" fill="#8A4E20">responds well</text><text x="580" y="584" text-anchor="middle" fill="#6E7F8C">poor</text>
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<text x="30" y="626" font-size="13" font-weight="700" fill="#23303A">3 · What's in TCGA, and what the engine uses</text>
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<text x="46" y="656" font-size="11" fill="#23303A"><tspan font-weight="700">Gene expression — the engine reads THIS.</tspan> Visible: immune ↑ (CD8A…), and MLH1 ↓ (it is</text>
<text x="46" y="673" font-size="11" fill="#23303A">silenced → findable). TMB &amp; MSI come in as per-patient labels.</text>
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<text x="46" y="712" font-size="11" fill="#8A4E20"><tspan font-weight="700">Invisible to expression:</tspan> MSH2 / MSH6 / PMS2 break by MUTATION, not silencing — their</text>
<text x="46" y="729" font-size="11" fill="#8A4E20">expression doesn't change, so they can't be found from expression. (Why only MLH1 surfaces.)</text>
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