Abstract 3739
Background
Endometrial cancer (EC) is one of the most common gynaecological tumours. Tumour mutational burden (TMB) has emerged as a promising predictor to evaluate efficacy to immunotherapy in several kinds of solid tumours. However, the relationship between TMB and genetic features of EC remains unclear.
Methods
Total 50 EC patients including 41 endometrioid adenocarcinoma, 6 uterine serous adenocarcinoma, 1 uterine clear cell carcinoma, 1 endometrial squamous cell carcinoma and 1 endometrial adenosquamous carcinoma were enrolled in this study. The ECs had been classified as FIGO I (n = 14), II (n = 6), III (n = 12), IV (n = 16) and not available (n = 2). FFPE tumour and matched blood samples were collected from patients for NGS-based targeted panel sequencing (450 genes). Genomic alterations and TMB were assessed.
Results
The 50 patients had a median age of 56 years (range, 32-73 years) with a median TMB of 3.8 muts/Mb (interquartile range (IQR), 1.5-13.7 muts/Mb). We found recurrent mutations, including PTEN (64%), PIK3CA (44%), ARID1A (40%), PIK3R1 (36%), TP53 (32%), CHD4 (20%), and KRAS (20%). FGFR2 mutations were occurred in 7 (14%) patients. The most frequently mutated genes in early-stage (FIGO I and II) were PTEN (85%), ARID1A (50%), PIK3R1 (50%), PIK3CA (40%), LRP1B (30%), and CHD4 (30%), while the most common mutations in advanced-stage (FIGO III and IV) were PTEN (46%), PIK3CA (43%), TP53 (43%), ARID1A (36%), PIK3R1 (29%), and KRAS (21%). We also found that all POLE mutations (5/5) occurred in early-stage. Mutations of PIK3R1, CHD4, CTCF, SETD2, PPP2R1A, NF1, BRCA2, ARID1B and POLE were associated with TMB-high (TMB-H, TMB≥10muts/Mb) (P < 0.05 for all). Importantly, all POLE mutations occurred in EC with TMB-H, including two cases of EC with ultrahigh TMB (TMB > 100 muts/Mb). At least one actionable mutation was identified in 86% (43/50) patients.
Conclusions
PI3K signaling pathway genes, PTEN, PIK3CA and PIK3R1 were most frequently mutated in EC. 26% patients (13/50) had TMB-H. POLE mutations likely occurred in early stage and were related with TMB-H, which may provide potential targets for immunotherapy of EC.
Clinical trial identification
Editorial acknowledgement
This study was supported by National Natural Science Foundation of China (Youth fund project, no. 81602267).
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China (Youth fund project, no. 81602267).
Disclosure
Y. Zhang: Full / Part-time employment: OrigiMed. S. Zhang: Full / Part-time employment: OrigiMed. S. Zhao: Full / Part-time employment: OrigiMed. F. Guo: Full / Part-time employment: OrigiMed. F. Pang: Full / Part-time employment: OrigiMed. L. Zhang: Full / Part-time employment: OrigiMed. X. Dong: Full / Part-time employment: OrigiMed. K. Wang: Full / Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.
Resources from the same session
2037 - Updated survival analysis of the randomized phase III trial comparing S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (SALTO) by the Dutch Colorectal Cancer Group.
Presenter: Johannes Kwakman
Session: Poster Display session 2
Resources:
Abstract
3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.
Presenter: Keisuke Kazama
Session: Poster Display session 2
Resources:
Abstract
3183 - Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase 2 study
Presenter: Akitaka Makiyama
Session: Poster Display session 2
Resources:
Abstract
3233 - Biweekly TAS-102 and Bevacizumab as a Third-Line Chemotherapy for metastatic colorectal cancer: A Phase II Multicenter Clinical Trial (TAS-CC4 study)
Presenter: Yoichiro Yoshida
Session: Poster Display session 2
Resources:
Abstract
5907 - Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer
Presenter: Pashtoon Kasi
Session: Poster Display session 2
Resources:
Abstract
1866 - Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer
Presenter: Emilie Moati
Session: Poster Display session 2
Resources:
Abstract
2312 - High Circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab
Presenter: Jakob Schou
Session: Poster Display session 2
Resources:
Abstract
5602 - Clinical relevance of circulating tumor (ct)DNA genotyping for first line cetuximab-based treatment monitoring in metastatic colorectal cancer (mCRC): a prospective multicentric study
Presenter: JOANA Vidal Barrull
Session: Poster Display session 2
Resources:
Abstract
3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Presenter: Beili Wang
Session: Poster Display session 2
Resources:
Abstract
5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells
Presenter: Anastasia Sitkovskaya
Session: Poster Display session 2
Resources:
Abstract