Details

Autor(en) / Beteiligte

• Nones, Katia
• Waddell, Nicola
• Wayte, Nicci
• Patch, Ann-Marie
• Bailey, Peter
• Newell, Felicity
• Holmes, Oliver
• Fink, J Lynn
• Quinn, Michael C J
• Tang, Yue Hang
• Lampe, Guy
• Quek, Kelly
• Loffler, Kelly A
• Manning, Suzanne
• Idrisoglu, Senel
• Miller, David
• Xu, Qinying
• Waddell, Nick
• Wilson, Peter J
• Bruxner, Timothy J C
• Christ, Angelika N
• Harliwong, Ivon
• Nourse, Craig
• Nourbakhsh, Ehsan
• Anderson, Matthew
• Kazakoff, Stephen
• Leonard, Conrad
• Wood, Scott
• Simpson, Peter T
• Reid, Lynne E
• Krause, Lutz
• Hussey, Damian J
• Watson, David I
• Lord, Reginald V
• Nancarrow, Derek
• Phillips, Wayne A
• Gotley, David
• Smithers, B Mark
• Whiteman, David C
• Hayward, Nicholas K
• Campbell, Peter J
• Pearson, John V
• Grimmond, Sean M
• Barbour, Andrew P

Titel

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Ist Teil von

• Nature communications, 2014-10, Vol.5 (1), p.5224-5224, Article 5224

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.