Breast Cancer — Broad WES/WGS (brca_broad)

Overview

A cohort of 108 primary, treatment-naive breast carcinoma/normal DNA pairs (patients from Mexico n=54 and Vietnam n=49) assembled by the Broad Institute. 103 pairs underwent whole-exome sequencing (33 Mb target, median 85.1% bases at ≥30x) and 22 pairs underwent whole-genome sequencing at 30x. Mutation calling used MutSig; copy-number used ABSOLUTE/HAPSEG; rearrangements were called with dRanger. An additional 235 samples were screened for the MAGI3-AKT3 fusion by RT-PCR.

Composition

  • 103 primary breast tumors with matched normal DNA for WES; 22 pairs with WGS.
  • Subtypes represented: Luminal A, Luminal B, HER2-enriched, basal-like.
  • Cancer type: BRCA.

Assays / panels (linked)

  • whole-exome-seq — 33 Mb target, median 85.1% at 30x.
  • whole-genome-seq — 30x, 22 pairs; structural variant discovery.
  • mutsig — statistical identification of significantly mutated genes.

Papers using this cohort

  • PMID:22722202 — Comprehensive genomic characterization of breast cancer (Banerji et al., 2012).

Notable findings derived from this cohort

  • Six significantly mutated genes (FDR < 0.1): TP53 (27%), PIK3CA (27%), AKT1 (6%), GATA3 (4%), MAP3K1 (3%), CBFB (4%) PMID:22722202.
  • CBFB identified as significantly mutated in breast cancer for the first time — 4 ER+ samples with truncating mutations PMID:22722202.
  • Recurrent MAGI3-AKT3 fusion found in 8/235 (3.4%) additional samples, including 5/72 (6.9%) triple-negative cases; represents an activating in-frame fusion kinase PMID:22722202.
  • AKT1 and PIK3CA mutations were mutually exclusive; combined PI3K pathway activation in ~33% of tumors PMID:22722202.
  • ERBB2 activating S310F mutations found in 2 samples without ERBB2 amplification PMID:22722202.
  • GSK-690693 (AKT inhibitor) and MK-2206 tested as potential therapeutic options targeting AKT pathway alterations including the MAGI3-AKT3 fusion PMID:22722202.

Sources

This page was processed by entity-page-writer on 2026-05-06.