Breast_Cancer_Somatic_Genetics_Study_

We propose to definitively characterise the somatic genetics of ER+ve, HER2-ve breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

12 Datasets 12 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001000138	The expression data for this study can be found here: http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1088/and its SNP6 data can be found here:http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1087/	Illumina Genome Analyzer II Illumina HiSeq 2000	58
EGAD00001000898	Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant.	Illumina HiSeq 2000	42
EGAD00001001322	A comprehensive characterisation and analysis of human breast cancers through whole-genome sequencing.	Illumina HiSeq 2000	196
EGAD00001001337	We propose to definitively characterise the somatic genetics of breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.	Illumina HiSeq 2000 Illumina HiSeq 2500 Illumina MiSeq	607
EGAD00001001338	We propose to definitively characterise the somatic genetics of breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.	Illumina Genome Analyzer II Illumina HiSeq 2000	49
EGAD00001001350	Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells	Illumina HiSeq 2000	8
EGAD00001002237	The disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription; co-ordinated secondary alterations in transcriptional pathways; and increased transcriptional noise. To catalogue the rules governing how somatic mutation Overall, 59% of 6980 exonic substitutions were expressed. Compared to other classes, nonsense mutations showed lower expression levels than expected with patterns characteristic of nonsense-mediated decay. 14% of 4234 genomic rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusion transcripts and premature poly-adenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes may drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data therefore reveals the rules by which transcriptional machinery interprets somatic mutation.	Illumina Genome Analyzer II Illumina HiSeq 2000	59
EGAD00001002696	Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling.	HiSeq X Ten Illumina HiSeq 2000	58
EGAD00001002740	We propose to definitively characterise the somatic genetics of breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing.	Illumina HiSeq 2000 Illumina HiSeq 2500 Illumina MiSeq	164
EGAD00010000915	Affymetrix SNP6.0 breast cancer genome sequencing data	Affymetrix SNP6.0	344
EGAD00010000917	399 tumors profiled using Agilent miRNA microarrays (Product Number G4872A, design ID 046064). The arrays are based on miRBase release 19.0 and 2006 human miRNAs are represented. 150 ng total RNA was used as input.	Agilent miRNA microarrays	399
EGAD00010001079	Affymetrix SNP6.0 array breast cancer data	Affymetrix SNP6.0	66

Publications	Citations
Subclonal diversification of primary breast cancer revealed by multiregion sequencing. Yates LR, Gerstung M, Knappskog S, Desmedt C, Gundem G, Van Loo P, Aas T, Alexandrov LB, Larsimont D, Davies H, Li Y, Ju YS, Ramakrishna M, Haugland HK, Lilleng PK, Nik-Zainal S, McLaren S, Butler A, Martin S, Glodzik D, Menzies A, Raine K, Hinton J, Jones D, Mudie LJ, Jiang B, Vincent D, Greene-Colozzi A, Adnet PY, Fatima A, Maetens M, Ignatiadis M, Stratton MR, Sotiriou C, Richardson AL, Lønning PE, Wedge DC, Campbell PJ. Nat Med 21: 2015 751-759	498
Mutational signatures of ionizing radiation in second malignancies. Behjati S, Gundem G, Wedge DC, Roberts ND, Tarpey PS, Cooke SL, Van Loo P, Alexandrov LB, Ramakrishna M, Davies H, Nik-Zainal S, Hardy C, Latimer C, Raine KM, Stebbings L, Menzies A, Jones D, Shepherd R, Butler AP, Teague JW, Jorgensen M, Khatri B, Pillay N, Shlien A, Futreal PA, Badie C, ICGC Prostate Group, McDermott U, Bova GS, Richardson AL, Flanagan AM, Stratton MR, Campbell PJ. Nat Commun 7: 2016 12605	126
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Davies H, Glodzik D, Morganella S, Yates LR, Staaf J, Zou X, Ramakrishna M, Martin S, Boyault S, Sieuwerts AM, Simpson PT, King TA, Raine K, Eyfjord JE, Kong G, Borg Å, Birney E, Stunnenberg HG, van de Vijver MJ, Børresen-Dale AL, Martens JW, Span PN, Lakhani SR, Vincent-Salomon A, Sotiriou C, Tutt A, Thompson AM, Van Laere S, Richardson AL, Viari A, Campbell PJ, Stratton MR, Nik-Zainal S. Nat Med 23: 2017 517-525	534
Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy. Caswell-Jin JL, McNamara K, Reiter JG, Sun R, Hu Z, Ma Z, Ding J, Suarez CJ, Tilk S, Raghavendra A, Forte V, Chin SF, Bardwell H, Provenzano E, Caldas C, Lang J, West R, Tripathy D, Press MF, Curtis C. Nat Commun 10: 2019 657	32
A practical framework and online tool for mutational signature analyses show inter-tissue variation and driver dependencies. Degasperi A, Amarante TD, Czarnecki J, Shooter S, Zou X, Glodzik D, Morganella S, Nanda AS, Badja C, Koh G, Momen SE, Georgakopoulos-Soares I, Dias JML, Young J, Memari Y, Davies H, Nik-Zainal S. Nat Cancer 1: 2020 249-263	131
Pan-cancer landscape of homologous recombination deficiency. Nguyen L, W M Martens J, Van Hoeck A, Cuppen E. Nat Commun 11: 2020 5584	227
Substitution mutational signatures in whole-genome-sequenced cancers in the UK population. Degasperi A, Zou X, Amarante TD, Martinez-Martinez A, Koh GCC, Dias JML, Heskin L, Chmelova L, Rinaldi G, Wang VYW, Nanda AS, Bernstein A, Momen SE, Young J, Perez-Gil D, Memari Y, Badja C, Shooter S, Czarnecki J, Brown MA, Davies HR, Genomics England Research Consortium, Nik-Zainal S. Science 376: 2022 science.abl9283	98
Spatial genomics maps the structure, nature and evolution of cancer clones. Lomakin A, Svedlund J, Strell C, Gataric M, Shmatko A, Rukhovich G, Park JS, Ju YS, Dentro S, Kleshchevnikov V, Vaskivskyi V, Li T, Bayraktar OA, Pinder S, Richardson AL, Santagata S, Campbell PJ, Russnes H, Gerstung M, Nilsson M, Yates LR. Nature 611: 2022 594-602	54
ERα-associated translocations underlie oncogene amplifications in breast cancer. Lee JJ, Jung YL, Cheong TC, Espejo Valle-Inclan J, Chu C, Gulhan DC, Ljungström V, Jin H, Viswanadham VV, Watson EV, Cortés-Ciriano I, Elledge SJ, Chiarle R, Pellman D, Park PJ. Nature 618: 2023 1024-1032	30
Quantitative and qualitative mutational impact of ionizing radiation on normal cells. Youk J, Kwon HW, Lim J, Kim E, Kim T, Kim R, Park S, Yi K, Nam CH, Jeon S, An Y, Choi J, Na H, Lee ES, Cho Y, Min DW, Kim H, Kang YR, Choi SH, Bae MJ, Lee CG, Kim JG, Kim YS, Yu T, Lee WC, Shin JY, Lee DS, Kim TY, Ku T, Kim SY, Lee JH, Koo BK, Lee H, Yi OV, Han EC, Chang JH, Kim KS, Son TG, Ju YS. Cell Genom 4: 2024 100499	2
A deep-learning-based genomic status estimating framework for homologous recombination deficiency detection from low-pass whole genome sequencing. Liu Y, Bi X, Leng Y, Chen D, Wang J, Ma Y, Zhang MZ, Han BW, Li Y. Heliyon 10: 2024 e26121	0
Prediction of homologous recombination deficiency identifies colorectal tumors sensitive to PARP inhibition. Corti G, Buzo K, Berrino E, Miotto M, Aquilano MC, Lentini M, Bellomo SE, Lorenzato A, Bartolini A, Mauri G, Lazzari L, Russo M, Di Nicolantonio F, Siena S, Marsoni S, Marchiò C, Bardelli A, Arena S. NPJ Precis Oncol 8: 2024 231	0