METABRIC: Data from Pereira et al (2016), The somatic mutation profiles of 2433 breast cancers refine their genomic and transcriptomic landscapes. Nat Comms 7.

The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2433 primary breast tumours that have copy number aberration (CNA), gene expression, and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters, and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intratumour heterogeneity using mutant allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13-14 or 8q24). High levels of intratumour heterogeneity are in general associated with worse outcome, but highly aggressive tumours with 11q13-14 amplification have low levels of intratumour heterogeneity. These results emphasise the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 14 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001002115	Targeted sequencing of 173 genes in 2433 primary breast tumours. Data includes 2433 tumour samples, 523 adjacent normal (breast) samples and 127 blood samples. Libraries were prepared with Illumina's Nextera custom enrichment kit targetting all the exons of the most frequently mutated breast cancer genes. Libraries were multiplexed (48 libraries per lane) and sequenced on Illumina HiSeq 2000 (100bp paired-end reads). Somatic mutations were calling with a custom pipeline. We identified 40 mutation-driver (Mut-driver) genes, and determined associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assessed the clonal states of Mut-driver mutations, and estimated levels of intra-tumour heterogeneity using mutant-allele fractions. The results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. Referece: Pereira et al. (2016) The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nature Communications		3083

Publications	Citations
The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, Tsui DW, Liu B, Dawson SJ, Abraham J, Northen H, Peden JF, Mukherjee A, Turashvili G, Green AR, McKinney S, Oloumi A, Shah S, Rosenfeld N, Murphy L, Bentley DR, Ellis IO, Purushotham A, Pinder SE, Børresen-Dale AL, Earl HM, Pharoah PD, Ross MT, Aparicio S, Caldas C. Nat Commun 7: 2016 11479	1105
High Densities of Tumor-Associated Plasma Cells Predict Improved Prognosis in Triple Negative Breast Cancer. Yeong J, Lim JCT, Lee B, Li H, Chia N, Ong CCH, Lye WK, Putti TC, Dent R, Lim E, Thike AA, Tan PH, Iqbal J. Front Immunol 9: 2018 1209	89
A subgroup of microRNAs defines PTEN-deficient, triple-negative breast cancer patients with poorest prognosis and alterations in RB1, MYC, and Wnt signaling. Wang DY, Gendoo DMA, Ben-David Y, Woodgett JR, Zacksenhaus E. Breast Cancer Res 21: 2019 18	29
Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer. Yeong J, Lim JCT, Lee B, Li H, Ong CCH, Thike AA, Yeap WH, Yang Y, Lim AYH, Tay TKY, Liu J, Wong SC, Chen J, Lim EH, Iqbal J, Dent R, Newell EW, Tan PH. J Immunother Cancer 7: 2019 34	68
Enhanced hexosamine metabolism drives metabolic and signaling networks involving hyaluronan production and O-GlcNAcylation to exacerbate breast cancer. Chokchaitaweesuk C, Kobayashi T, Izumikawa T, Itano N. Cell Death Dis 10: 2019 803	28
Molecular stratification within triple-negative breast cancer subtypes. Wang DY, Jiang Z, Ben-David Y, Woodgett JR, Zacksenhaus E. Sci Rep 9: 2019 19107	81
Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis. Ramchandani D, Berisa M, Tavarez DA, Li Z, Miele M, Bai Y, Lee SB, Ban Y, Dephoure N, Hendrickson RC, Cloonan SM, Gao D, Cross JR, Vahdat LT, Mittal V. Nat Commun 12: 2021 7311	133
Spectrum of <i>MAP3K1</i> mutations in breast cancer is luminal subtype-predominant and related to prognosis. Li C, Zhang G, Wang Y, Chen B, Li K, Cao L, Ren C, Wen L, Jia M, Mok H, Lai J, Xiao W, Li X, Liao N. Oncol Lett 23: 2022 68	6
Breast tumor microenvironment structures are associated with genomic features and clinical outcome. Danenberg E, Bardwell H, Zanotelli VRT, Provenzano E, Chin SF, Rueda OM, Green A, Rakha E, Aparicio S, Ellis IO, Bodenmiller B, Caldas C, Ali HR. Nat Genet 54: 2022 660-669	129
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant. Correia L, Magno R, Xavier JM, de Almeida BP, Duarte I, Esteves F, Ghezzo M, Eldridge M, Sun C, Bosma A, Mittempergher L, Marreiros A, Bernards R, Caldas C, Chin SF, Maia AT. NPJ Breast Cancer 8: 2022 71	4
ABL kinases regulate translation in HER2+ cells through Y-box-binding protein 1 to facilitate colonization of the brain. McKernan CM, Khatri A, Hannigan M, Child J, Chen Q, Mayro B, Snyder D, Nicchitta CV, Pendergast AM. Cell Rep 40: 2022 111268	3
Turning up a new pattern: Identification of cancer-associated fibroblast-related clusters in TNBC. Xie J, Zheng S, Zou Y, Tang Y, Tian W, Wong CW, Wu S, Ou X, Zhao W, Cai M, Xie X. Front Immunol 13: 2022 1022147	31
Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer. Jiang Z, Ju Y, Ali A, Chung PED, Skowron P, Wang DY, Shrestha M, Li H, Liu JC, Vorobieva I, Ghanbari-Azarnier R, Mwewa E, Koritzinsky M, Ben-David Y, Woodgett JR, Perou CM, Dupuy A, Bader GD, Egan SE, Taylor MD, Zacksenhaus E. Nat Commun 14: 2023 4313	6
Multi-omics analyses unravel DNA damage repair-related clusters in breast cancer with experimental validation. Liu P, Deng X, Zhou H, Xie J, Kong Y, Zou Y, Yang A, Li X. Front Immunol 14: 2023 1297180	9