APOBEC3B Upregulation and Genomic Mutation Patterns in Serous Ovarian Carcinoma

作者：Leonard Brandon; Hart Steven N; Burns Michael B; Carpenter Michael A; Temiz Nuri A; Rathore Anurag; Vogel Rachel I; Nikas Jason B; Law Emily K; Brown William L; Li Ying; Zhang Yuji; Maurer Matthew J; Oberg Ann L; Cunningham Julie M; Shridhar Viji; Bell Debra A; April Craig; Bentley David; Bibikova Marina; Cheetham R Keira; Fan Jian Bing; Grocock Russell; Humphray Sean; King**ury Zoya; Peden John; Chien Jeremy; Swisher Elizabeth M; Hartmann Lynn C

来源：Cancer Research, 2013, 73(24): 7222-7231.

DOI：10.1158/0008-5472.CAN-13-1753

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5%26apos;-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C- to-A and C- to-G transversion mutations within 5%26apos;-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA %26quot;repair%26quot; enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability.

• 出版日期2013-12-15