Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma

A partir de données issues du projet "The Cancer Genome Atlas", puis menée sur 2 cohortes indépendantes de 43 et 40 patientes atteintes d'un carcinome invasif du sein, cette étude identifie des événements d'épissage alternatif de 5 gènes en association avec 3 sous-types de cancer du sein (ER+ HER2-, ER- HER2- et HER2+)

Résumé en anglais

Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2−, ER− HER2−, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2− and ER− HER2− primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2− and ER− HER2− patients, showing that these events were truly subtype specific.