The prognostic effects of somatic mutations in ER-positive breast cancer.
MetadataShow full item record
Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.
Version of record
MAP Kinase Kinase Kinase 1
Class I Phosphatidylinositol 3-Kinases
Discoidin Domain Receptor 1
License start date
Nature communications, 2018, 9 (1), pp. 3476 - ?
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Showing items related by title, author, creator and subject.
A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours. Jamieson, D; Griffin, MJ; Sludden, J; Drew, Y; Cresti, N; Swales, K; Merriman, M; Allen, R; Bevan, P; Buerkle, M; Mala, C; Coyle, V; Rodgers, L; Dean, E; Greystoke, A; Banerji, U; Wilson, RH; Evans, TRJ; Anthoney, A; Ranson, M; Boddy, AV; Plummer, R (2016-11)<h4>Purpose</h4>We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 ...
D'Abaco, GM; Hooper, S; Paterson, H; Marshall, CJ (2002-12)The Ras GTPase is a critical transducer of mitogenic signals ultimately leading to inactivation of the retinoblastoma (Rb) protein, but the molecular basis underlying Ras-dependent control of cell cycle kinetics remains ...
Activation of either ERK1/2 or ERK5 MAP kinase pathways can lead to disruption of the actin cytoskeleton. Barros, JC; Marshall, CJ (2005-04)Oncogenic transformation often leads to the disruption of the actin cytoskeleton. Activation of the classical Ras-Raf-MEK1/2-ERK1/2 signalling cascade has been implicated in the effects of oncogenes such as Ras and Src on ...