TCGA Breast Invasive Carcinoma (TCGA, Nature 2012)

Overview

Landmark multi-platform molecular characterization of 825 primary breast cancers assembled by The Cancer Genome Atlas (TCGA) Network and published in Nature (2012). The study integrated six genomic and proteomic platforms to define the molecular landscape of breast cancer across its major subtypes.

Composition

• 825 patients with primary breast cancer; 466 tumors assayed across 5 platforms, 348 across all 6 platforms.
• Cancer type: BRCA.
• Platforms: Agilent mRNA expression microarrays (n=547), Illumina 450k methylation arrays (n=802), Affymetrix SNP 6.0 (n=773), microRNA sequencing (n=697), whole-exome sequencing (n=507), Reverse Phase Protein Arrays (n=403).
• PAM50 classifier used for mRNA subtype assignment.

Assays / panels (linked)

• Whole-exome sequencing — 507 tumors, somatic mutation discovery.
• Affymetrix SNP 6.0 — 773 tumors, somatic copy number alterations.
• Illumina 450k methylation array — 802 tumors, DNA methylation profiling.
• RNA-seq — microRNA sequencing of 697 tumors.

Papers using this cohort

• PMID:23000897 — Comprehensive molecular portraits of human breast tumors (TCGA, Nature 2012).

Notable findings derived from this cohort

• 35 significantly mutated genes identified from 510 tumor WES; only TP53, PIK3CA, and GATA3 mutated at >10% across all subtypes PMID:23000897.
• Four molecular subtypes (Luminal A, Luminal B, HER2-Enriched, Basal-like) confirmed with distinct mutational spectra and copy number landscapes PMID:23000897.
• Basal-like breast cancers share striking molecular features with HGSOC including TP53 mutations, RB1/BRCA1 loss, and MYC amplification PMID:23000897.
• ~20% of Basal-like tumors carry germline and/or somatic BRCA1/BRCA2 variants, identifying a population potentially amenable to olaparib and platinum therapy PMID:23000897.
• Cross-species transcriptome concordance: 297 of 1,469 genes up-regulated in rat Pik3caH1047R/Tp53Indel tumors also enriched in TCGA PIK3CA+TP53 vs PIK3CA-only/WT-TP53 breast cancers (Fisher’s p<1×10^-14) PMID:26437033
• Used as the 772-sample primary breast cancer reference cohort (419 HR+/HER2−, 100 HR−/HER2−, 145 HER2+) for comparison against 216 metastatic breast cancers; APOBEC signatures (2+13) contributed 31.9% of mutations in HR+/HER2− primary samples vs 58.8% in HR+/HER2− metastatic tumors (p<2e-16) PMID:28027327

Sources

• PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:26437033

This page was processed by crosslinker on 2026-05-14. - PMID:28027327

This page was processed by wiki-cli on 2026-05-14.