Seeing What Matters — Composite Diagnostics (Imaging × Transcriptome × CNV)

Therapy moves only when we can answer “for whom, when, and what.” This chapter maps a beginner-friendly framework for composite diagnostics across imaging, transcriptomic states, and copy-number signatures.

Today’s Goals (3-Minute Preview)

• Grasp the core molecular panel (MGMT, EGFR, TERT, PTEN, etc.).
• Understand GBM-typical CNV signatures (chr7 gain/chr10 loss) and the pre-CC signature.
• See what emerges by combining imaging (DTI, etc.) × molecular reads.
• Adopt a lightweight reporting template you can use immediately.

Core Markers: The Minimum Viable Panel

Pathology & Molecular (Basics)

• MGMT promoter methylation: temozolomide sensitivity.
• TERT promoter mutations: common in adult GBM.
• EGFR amplification/variants: e.g., EGFRvIII; growth signaling.
• PTEN loss: PI3K–AKT axis activation.
• IDH: most primary adult GBM are IDH-wildtype.

Copy-Number (CNV) & Signatures

• chr7 gain / chr10 loss (7+/10−): hallmark GBM combination.
• EGFR amp (7p) / PTEN loss (10q) often co-occur.
• pre-CC signature: early alterations shared with the tumor mass.

Start with MGMT + CNV (7+/10−) + EGFR/TERT/PTEN; expand as your center allows.

Transcriptomic “Faces”: OPC/AC/MES (Implementation of Part 5)

Use gene-set signatures rather than single genes to classify states.

OPC-like

High cell cycleDNA synthesisWEE1-sensitive contexts

AC-like

Glial/metabolicContext-specific dependencies

MES-like

Inflammation/ECMInvasive/resistantMicroenvironment-linked

States form a continuum; therapy and milieu can tilt the balance (plasticity).

Composite Diagnostics: Imaging × Molecular

Imaging (examples)

• DTI for fiber orientations → invasion pathways.
• Contrast kinetics for angiogenesis/BBB leakage.
• Texture metrics to quantify heterogeneity.

Molecular (examples)

• 7+/10− with EGFR/PTEN for pathway dominance.
• pre-CC signature for SVZ “seed” contribution.
• OPC/AC/MES signatures for plasticity direction.

Interpretation Patterns

Finding	Hypothesis	Therapeutic Hint
DTI shows tract-aligned spread	Established invasion routes	Anti-invasion (ECM/adhesion) + anti-proliferation
7+/10− + EGFR amplification	Growth/signal dominance	Standard backbone + pathway control (trial contexts)
High pre-CC signature	Large “seed” contribution	Early intervention + microenvironment (MIF–CD74)
MES-skewed signature	Invasive/resistant bias	Strengthen ECM/adhesion controls (+ cell cycle)
MGMT methylated	TMZ sensitivity	Expect benefit from SOC ± TTF where applicable

Caveats & Pitfalls

• Specimen quality and intratumoral heterogeneity shift results; re-biopsy at relapse when feasible.
• Imaging distortion from edema/necrosis; use multimodal corroboration.
• Signature drift under therapy (plasticity); track longitudinally.
• Access varies by country; infrastructure/interpretation differ (see Part 8).

Quick Summary

• MGMT + CNV (7+/10−) + EGFR/TERT/PTEN form the base.
• OPC/AC/MES + pre-CC readouts capture “face” and “seed.”
• Imaging × molecular alignment guides who/when/what.

My View

I read in layers: foundation (MGMT/CNV) → face (OPC/AC/MES) → seed (pre-CC) → niche (MIF–CD74) → pathway. That hierarchy makes it feasible to design fewer-move, deeper-reaching combinations. Next (Part 7), we’ll chart the global development landscape by modality.

Edited by the Morningglorysciences team.

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