{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Nicola Waddell"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000192"],"host":["EGA"],"description":["EGA DAC EGAC00001000192"],"repository":["EGA"],"email":["Nic.Waddell@qimrberghofer.edu.au"],"pubmed_abstract":["Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC."],"pubmed_title":["Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis."],"pubmed_authors":["Nones Katia K, Waddell Nicola N, Wayte Nicci N, Patch Ann-Marie AM, Bailey Peter P, Newell Felicity F, Holmes Oliver O, Fink J Lynn JL, Quinn Michael C J MCJ, Tang Yue Hang YH, Lampe Guy G, Quek Kelly K, Loffler Kelly A KA, Manning Suzanne S, Idrisoglu Senel S, Miller David D, Xu Qinying Q, Waddell Nick N, Wilson Peter J PJ, Bruxner Timothy J C TJC, Christ Angelika N AN, Harliwong Ivon I, Nourse Craig C, Nourbakhsh Ehsan E, Anderson Matthew M, Kazakoff Stephen S, Leonard Conrad C, Wood Scott S, Simpson Peter T PT, Reid Lynne E LE, Krause Lutz L, Hussey Damian J DJ, Watson David I DI, Lord Reginald V RV, Nancarrow Derek D, Phillips Wayne A WA, Gotley David D, Smithers B Mark BM, Whiteman David C DC, Hayward Nicholas K NK, Campbell Peter J PJ, Pearson John V JV, Grimmond Sean M SM, Barbour Andrew P AP"],"additional_accession":[]},"is_claimable":false,"name":"Whole Genome Sequencing of Esophageal Adenocarcinomas DAC","description":"Data Access Committee EGAC00001000192","dates":{"output":"2025-1-9"},"accession":"EGAC00001000192","cross_references":{"TAXONOMY":["9606"],"pubmed":["25351503"],"EGA":["EGAS00001000750","EGAD00001000845"]}}