A pancancer analysis of CDK12 alterations in Chinese population.

e15068 Background: Cyclin-dependent kinases ( CDKs) are key regulators of both cell cycle progression and transcription. Analysis of mutation detection of CDK12 in pan-cancer could contribute to understand the complexity and diversity of genetic alterations present in CDK12 mutant cancers. Herein, we provide a pan-cancer analysis of CDK12 alterations in Chinese population. Methods: Using gene-panel target-capture next generation sequencing, we analyzed 17509 tumor tissue or plasma ctDNA samples from different patients. Testing included analysis of single nucleotide variants, insertions/deletions, fusions and amplifications. CDK12 variants of uncertain significance and synonymous variants excluded. Results: In total, 0.95% (167/17509) of pan-cancer patients harbored CDK12 mutation, and 32 patients carried at least two CDK12 mutations. The most common genetic alteration type was truncating mutations (128, 64%), followed by amplications (53, 26%), missense mutations (9, 5%) and splicing mutations (9, 5%). In our cohort, the highest CDK12 mutation frequency tumor type was prostate cancer(11.30%), followed by breast cancer (3.96%), bladder cacner (3.16%), stomach cancer (1.84%) and colorectal cacner (1.13%). The TCGA pan-cancer cohort confirmed that the CDK12-altered cancer was associated with shorter overall survival (81.11 vs 133.00 mos, p = 5.30×10 −18 ) in prostate cancer. Tumor mutation burdens(TMB) were calculated for 137 samples of all the 167 samples. The median TMB was 7.66 mut/Mb with 38%≥10 mut/Mb and 17%≥20 mut/Mb. including a patient with hypermutated in colorectal cancer(TMB: 88.24 Mut/Mb), harboring three CDK12 mutations. Conclusions: Genomic alterations in CDK12 are widespread among Chinese patients, with alteration rates and alteration types varying by cancer type. We identified prostate cancer as the cancer type with the highest prevalence of CDK12 oncogenic alterations. Additional analyses are ongoing.