American Association for Cancer Research
00085472can152128-sup-152923_2_supp_3283925_nztysz.pdf (215.66 kB)

Supplementary Methods from Ovarian Cancers Harboring Inactivating Mutations in CDK12 Display a Distinct Genomic Instability Pattern Characterized by Large Tandem Duplications

Download (215.66 kB)
journal contribution
posted on 2023-03-30, 23:47 authored by Tatiana Popova, Elodie Manié, Valentina Boeva, Aude Battistella, Oumou Goundiam, Nicholas K. Smith, Christopher R. Mueller, Virginie Raynal, Odette Mariani, Xavier Sastre-Garau, Marc-Henri Stern

Supplementary Materials and Methods and References


Institut National de la Santé et de la Recherche Médicale, Cancéropôle Ile-de-France, INCa, Institut Curie and its Translational Research Department



CDK12 is a recurrently mutated gene in serous ovarian carcinoma, whose downregulation is associated with impaired expression of DNA damage repair genes and subsequent hypersensitivity to DNA-damaging agents and PARP1/2 inhibitors. In this study, we investigated the genomic landscape associated with CDK12 inactivation in patients with serous ovarian carcinoma. We show that CDK12 loss was consistently associated with a particular genomic instability pattern characterized by hundreds of tandem duplications of up to 10 megabases (Mb) in size. Tandem duplications were characterized by a bimodal (∼0.3 and ∼3 Mb) size distribution and overlapping microhomology at the breakpoints. This genomic instability, denoted as the CDK12 TD-plus phenotype, is remarkably distinct from other alteration patterns described in breast and ovarian cancers. The CDK12 TD-plus phenotype was associated with a greater than 10% gain in genomic content and occurred at a 3% to 4% rate in The Cancer Genome Atlas–derived and in-house cohorts of patients with serous ovarian carcinoma. Moreover, CDK12-inactivating mutations together with the TD-plus phenotype were also observed in prostate cancers. Our finding provides new insight toward deciphering the function of CDK12 in genome maintenance and oncogenesis. Cancer Res; 76(7); 1882–91. ©2016 AACR.