Abstract 1798P
Background
WEE1, as an important kinase in DNA damage response (DDR) pathway, is a potent therapeutic target in multiple cancers. Recently, multiple drugs targeting WEE1 are undergoing clinical trials. Although previous study has reported the frequency of WEE1 mutations across cancers in TCGA cohorts, little was known about the characteristics of WEE1 mutations in Chinese cancer patients. Thus, we aim to illustrate WEE1 mutations through genomic profiling in Chinese cancer patients, which may bring new insights for personalized disease management in these patients.
Methods
Genomic profiling was retrospectively analyzed on 54,354 patients across multiple cancers. Frequency of patients with WEE1 mutations was calculated among various cancers. The concurrent gene alteration and the distribution of mutations of WEE1 gene was evaluated.
Results
We identified totally 74 WEE1 mutations in about 0.14% (74/54,354) of Chinese multi-cancer cohort. WEE1 mutations occurred mostly in esophageal cancer (0.92%, 4/433), breast cancer (0.48, 3/629), gastric cancer (0.33%, 7/2131), and bowel cancer (0.22, 13/5980). There were no statistically significant differences in gender (49 in male and 24 in female, p=0.099) or age (59 in older group (> 40 years old) and 15 in younger group (<40 years old, p=0.11)) among patients with WEE1 mutations. In addition, the top five concurrent mutant homologous recombination repair (HRR) genes of WEE1 were TP53 (59.46%), ATM (35.14%), APC (33.78%), NF1 (31.08%) and SMARCA4 (28.38%). Moreover, the top frequent mutations of WEE1 were E43 deletion and R361/R639/E538 mutation. Furthermore, we identified the common mutation sites of WEE1 gene in both our and TCGA cohort were E583/E449/R581/A365/L213, indicating that these sites may be important for WEE1 kinase activity. Finally, we found that E43 deletion was the unique and the most frequently mutant site in our rather that TCGA cohort, which may serve as a novel kinase activity site of Chinese patients.
Conclusions
Our results revealed the characteristics of WEE1 mutation in a large cohort of Chinese multi-cancer patients, and we identified the concurrent HRR gene alterations and hotspot mutations of WEE1 gene, which may benefit these patients with personalized diagnoses and therapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Yuan, X. Zhang, D. Wang, H. Zhu: Financial Interests, Personal, Full or part-time Employment: Genetron Health (Beijing) Technology, Co. Ltd. All other authors have declared no conflicts of interest.