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
3082 - Prognostic and predictive role of body mass index (BMI) in metastatic colorectal cancer (mCRC): a pooled analisys of TRIBE and TRIBE-2 studies by GONO
Presenter: Emanuela Dell'Aquila
Session: Poster Display session 2
Resources:
Abstract
3618 - Drug holidays and overall survival in patients treated for metastatic colorectal cancer
Presenter: Silvio Ken Garattini
Session: Poster Display session 2
Resources:
Abstract
6111 - Quality of life during 1st-line FOLFOXIRI+/- panitumumab in RAS wild-type metastatic colorectal cancer: Results from the randomized VOLFI trial (AIO KRK-0109)
Presenter: Michael Geissler
Session: Poster Display session 2
Resources:
Abstract
1042 - A biomarker combination indicating resistance to FOLFOX plus bevacizumab in metastastic colorectal cancer : results of phase I of the PERMAD trial
Presenter: Thomas Seufferlein
Session: Poster Display session 2
Resources:
Abstract
3291 - Microsatellite Instability (MSI) status and prognosis in colorectal cancer: meta-analysis
Presenter: James Toh
Session: Poster Display session 2
Resources:
Abstract
2046 - Choosing the right strategy based on individualized treatment effect predictions: Combination versus sequential chemotherapy in patients with metastatic colorectal cancer.
Presenter: Miriam Koopman
Session: Poster Display session 2
Resources:
Abstract
2589 - Noninferiority on overall survival of every-2-weeks vs weekly schedule of cetuximab for first-line treatment of RAS wild-type metastatic colorectal cancer
Presenter: Stefan Kasper
Session: Poster Display session 2
Resources:
Abstract
4944 - POLAF study: Efficacy and safety of FOLFIRI/aflibercept in a phase II trial in patients with metastatic colorectal cancer: Results of plasmatic prognostic and predictive markers
Presenter: Maria Elena Elez Fernandez
Session: Poster Display session 2
Resources:
Abstract
2042 - The accuracy of the clinical PCI score in patients with peritoneal carcinomatosis of colorectal cancer
Presenter: Nadine De Boer
Session: Poster Display session 2
Resources:
Abstract
2667 - The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC).
Presenter: Takeshi Kawakami
Session: Poster Display session 2
Resources:
Abstract