RNA TargetsGynecologic OncologyResearch Use Only
Endometrial Cancer (EC)
Gene Expression Reference Targets
Gene Expression Reference Targets
A biologically curated RNA target reference for endometrial cancer spanning the four TCGA ProMisE molecular subtypes, mismatch repair/POLE biology, HER2/PI3K driver pathways, and immune checkpoint biology — enabling researchers to configure custom Tapestri assays for lenvatinib/pembrolizumab response stratification, POLE-hypermutated biology, and precision EC studies.
232
Total Genes
7
Functional Categories
4
TCGA Subtypes
6+
Curation Sources
1
Panel Power Scorecard & Functional Categories
● Panel Power Scorecard
Panel Score: 70 / 100
88%
Landmark
Biomarker
Coverage
Biomarker
Coverage
81%
COSMIC
Tier-1
Coverage
Tier-1
Coverage
8 genes
FDA
Biomarker
Genes
Biomarker
Genes
14 genes
Clinical Trial
Biomarkers
Biomarkers
7 states
Cell States
Resolvable
Resolvable
232 genes
Total Panel
Genes
Genes
Published precedent — targeted panels are sufficient
Makker et al. 2022 NEJM (KEYNOTE-775 lenvatinib+pembrolizumab)
Kandoth et al. 2013 Nature (TCGA EC molecular classification)
48
Subtype Drivers
42
MMR / POLE
40
HER2 / PI3K
48
Immune TME
36
Lineage
28
Stroma / EMT
20
Cell Cycle
2
Background & Curation Principles
Commercial Assays
- FoundationOne CDx (gynecologic)
- Tempus xT (solid tumor)
- Illumina TruSight Oncology 500
- QIAGEN QIAseq Endometrial Panel
Public Databases
- TCGA UCEC (373 tumors, ProMisE classification)
- COSMIC (endometrial mutations)
- MSigDB gynecologic signatures
- Human Cell Atlas (uterine)
- TISCH2 EC TME
Peer-Reviewed Literature
- TCGA molecular classification (Kandoth 2013 Nature)
- ProMisE simplified classifier (Kommoss 2018 JCO)
- Lenvatinib + pembrolizumab (KEYNOTE-775, Makker 2022 NEJM)
- POLE ultramutated = favorable IO prognosis (Stelloo 2015)
Why Single-Cell RNA for Endometrial Cancer?
The four ProMisE molecular subtypes have radically different immune TME compositions: POLE-ultramutated has the highest TIL infiltration of any cancer type; MSI-H has dense immune infiltration with functional TILs; p53-mutant serous is immune cold; NSMP is variable. Bulk RNA cannot determine which subtype a given cell belongs to. Tapestri co-detects POLE or TP53 mutation alongside T cell infiltration state per cell — directly linking molecular subtype to immune biology.
POLE Ultramutated — The Highest TMB Cancer
POLE-ultramutated EC has >100 mutations/Mb — the highest TMB of any cancer — driven by POLE proofreading domain mutations. Despite this extreme mutational burden, POLE-ultramutated EC has excellent prognosis and exceptional ICI response. Panel covers POLE/POLD1 mutations, MMR pathway genes (MLH1/MSH2/MSH6/PMS2), POLE-associated microsatellite markers, and the downstream T cell activation signatures that explain the favorable prognosis.
3
Target Reference Structure — Gene Table
1 · TCGA Molecular Subtypes / Driver2 · MMR / POLE / TMB3 · HER2 / PI3K Pathway4 · Immune TME / Checkpoint5 · Lineage / Histotype6 · Stroma / EMT7 · Cell Cycle
| Category | Representative Genes (n) | Biological Function | Disease Relevance | scD+R Use Case |
|---|---|---|---|---|
| 1 · TCGA Molecular Subtype Drivers · 48 genes | ||||
| Driver | TP53, CTNNB1, PIK3CA, PTEN, AKT1, KRAS, ARID1A, PIK3R1, RB1, CDKN2A, FBXW7, PPP2R1A, ERBB2, FGFR2, FGFR3, MYC, CCND1, CDK4, CDK6, MDM2 (20) + 28 accessory | p53/CTNNB1/PI3K oncogenic programs; HER2 amplification | TP53 = p53-mutant serous (worst prognosis); CTNNB1 = endometrioid; PIK3CA/PTEN = NSMP; HER2 (ERBB2) = serous (trastuzumab); FGFR2 = endometrioid | Co-detect TP53 mutation + p53-mutant transcriptional state per tumor cell |
| 2 · MMR / POLE / TMB Pathway · 42 genes | ||||
| DDR | MLH1, MSH2, MSH6, PMS2, EPCAM, POLE, POLD1, BRCA1, BRCA2, ATM, CHEK1, CHEK2, PARP1, RAD51, ERCC1, FANCA (16) + 26 accessory | MMR deficiency; POLE proofreading; HRD; TMB | MLH1/MSH2/MSH6/PMS2 = MMRd (pembrolizumab approved); POLE = ultramutated (best ICI response); BRCA1/2 = HRD/olaparib context | Identify MMRd vs POLE-mut vs HRD subclones; assess ICI eligibility per tumor cell |
| 3 · HER2 / PI3K / Signaling · 40 genes | ||||
| Signaling | ERBB2, ERBB3, PIK3CA, PIK3R1, PTEN, AKT1, AKT2, MTOR, TSC1, TSC2, RICTOR, KRAS, NRAS, HRAS, MAP2K1, FGFR2, FGFR3, VEGFA, KDR, ANGPT2 (20) + 20 accessory | HER2 dimerization; PI3K/mTOR; FGFR2; VEGF | HER2 = trastuzumab/tucatinib (serous EC); PI3K/mTOR = everolimus target; FGFR2 = infigratinib; VEGFA = lenvatinib target | Map HER2 expression per tumor cell; identify PI3K-hyperactive subpopulations |
| 4 · Immune TME / Checkpoint · 48 genes | ||||
| Immune | CD3E, CD8A, CD4, GZMB, IFNG, TOX, PDCD1, LAG3, HAVCR2, TIGIT, CD274, FOXP3, IL2RA, TCF7, CXCL13, TREM2, SPP1, CD68, CD163, B2M, HLA-A, IDO1 (22) + 26 accessory | TIL characterization; checkpoint expression; myeloid TME | POLE-ultramutated = highest TIL density of any cancer; CD274 = pembrolizumab/lenvatinib combination target; B2M loss = ICI resistance | Resolve functional vs exhausted TIL states; map immune landscape per ProMisE subtype |
| 5 · Lineage / Histotype Markers · 36 genes | ||||
| Lineage | ESR1, PGR, FOXA2, HOXA10, PAX8, CDH1, VIM, CDH2, SNAI2, ZEB1, TWIST1, EPCAM, KRT8, KRT18, MUC1, CEA (CEACAM5), CA125 (MUC16) (17) + 19 accessory | Endometrioid vs serous vs clear cell histotype | ESR1/PGR = endometrioid (medroxyprogesterone); PAX8 = gynecologic lineage marker; VIM = serous; CDH1 = endometrioid lineage | Classify histotype per tumor cell; identify hormone receptor expression for hormonal therapy eligibility |
| 6 · Stroma / EMT / Myometrial Invasion · 28 genes | ||||
| Stromal | ACTA2, FAP, PDGFRA, PDGFRB, TGFB1, CXCL12, COL1A1, MMP2, MMP9, POSTN, LRRC15, VIM, TWIST1, ZEB1 (14) + 14 accessory | CAF activation; myometrial invasion; EMT | TGFB1 = T cell exclusion (poor ICI response); deep myometrial invasion → lymph node metastasis; POSTN = invasive stroma | Identify invasive front stromal cells; map TGFβ-mediated immune exclusion in endometrium |
| 7 · Cell Cycle / Proliferation · 20 genes | ||||
| Cell Cycle | MKI67, TOP2A, AURKA, CCNB1, CDK2, E2F1, FOXM1, MCM2, PLK1, CDC20 (10) + 10 accessory | Proliferative index; WHO grade | MKI67 = FIGO grade; FOXM1 = serous EC aggression; CDK4/6 = palbociclib target (ER+ EC) | Score tumor cell proliferation; link to FIGO grade and metastatic risk |
Total: 232 genesCat 1: 48 · Cat 2: 42 · Cat 3: 40 · Cat 4: 48 · Cat 5: 36 · Cat 6: 28 · Cat 7: 20
ⓘ Select genes appear in more than one functional category reflecting their multi-role biology. The total above counts unique genes; per-category counts include all category-relevant entries.