Abstract 5213
Background
Anti-PD-1 monoclonal antibody monotherapy achieves poor outcomes in mucosal melanoma, but our previous study has demonstrated that primary malignant melanoma of esophagus (PMME) has a dramatically high response rate (ORR 75%). The genomic landscape of PMME and reasons for this finding have not been extensively investigated.
Methods
Whole exome sequencing were performed in seven treatment-naive PMME tumor samples and matched normal tissues, and genomic data of eight mucosal melanomas was obtained from the International Cancer Genome Consortium. Comprehensive profiling was performed to analyze the of genetic differences of PMME with mucosal melanoma.
Results
The mean depth of coverage was 268X (ranged from 100X to 400X), 1203 SNV/InDels were detected in seven PMME samples, with a mean value of 172 mutations. The median tumor mutation burden (TMB) was 3.58 mutations/Mb (range 0.19-9.58 mutations/Mb), which was significantly than mucosal melanoma (P = 0.021). The mutation spectrum of SNVs displayed more frequency of T>A transition while less frequency of C>T transversion compared to mucosal melanoma. There were 36 genes found to be mutated in more than two PMME tumor samples, and the most significantly mutated genes were CFH (42.9%, 3/7) and MUC16 (42.9%, 3/7). Both BRAF and NRAS were only found in one sample, and no NF1, KIT and SF3B1 mutation were detected. In total, 671 CNVs were detected, and the most frequently amplification chromosomal regions were 10q and 1p, while most frequently deletion in 1q and 8q. Genetic aberrations were mainly enriched in RTK/RAS and WNT pathways.
Conclusions
The TMB is higher in PMME compared to mucosal melanoma, with the highest mutation frequency in CFH and MUC16. CFH has a critical role in the regulation of complement activation, and MUC16 has been reported to be associated with higher tumor mutation load and outcomes in gastric cancer. In summary, our study reveals that the genomic landscape of PMME is different from mucosal melanoma originates from other mucosal membrane sites, and indicates that CFH and MUC16 mutation might be associated with better response to anti-PD-1 monoclonal antibody in PMME patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Peking University Cancer Hospital-Beijing Cancer Hospital.
Funding
Beijing Talents Foundation (2016000021223ZK18), National Natural Science Foundation of China (81672696, 81402264).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3517 - Role of follow-up (FU) FDG-PET/CT (FU-FDG-PET/CT) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) treated with chemotherapy and radiotherapy (RT), either concurrent (CRT) or sequential (ST).
Presenter: Bert Van Den Heuvel
Session: Poster Display session 3
Resources:
Abstract
5071 - Expression of estrogen receptor and programmed cell death-ligand 1 can be complementary prognostic factors in HPV-positive oropharyngeal squamous cell carcinoma
Presenter: Soohyeon Kwon
Session: Poster Display session 3
Resources:
Abstract
5306 - Real-world data of clinicopathologic characteristics of young oropharyngeal cancer patients.
Presenter: Maria Nieva
Session: Poster Display session 3
Resources:
Abstract
3407 - The clinical significance and biological mechanisms of miR-499a in high-tobacco exposed head and neck squamous cell carcinoma
Presenter: Shiqi Gong
Session: Poster Display session 3
Resources:
Abstract
3310 - Liquid biopsy for mutational profiling of locoregional recurrent and/or metastatic squamous cell carcinoma of the head and neck
Presenter: Rachel Galot
Session: Poster Display session 3
Resources:
Abstract
2362 - Blood-based testing of mutations in patients with Head and neck squamous cell carcinoma (HNSCC) using highly sensitive SafeSEQ technology
Presenter: Florentia Fostira
Session: Poster Display session 3
Resources:
Abstract
4533 - The head and neck Lung Immune Prognostic Index (HN-LIPI): a prognostic Score for Immune Checkpoint Inhibitors (ICI) in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) patients.
Presenter: Ruth Gabriela Herrera Gomez
Session: Poster Display session 3
Resources:
Abstract
5262 - Immune-related adverse events (irAEs) and outcome in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) patients (pts) treated by immune-checkpoints inhibitors (ICI)
Presenter: Neus Baste Rotllan
Session: Poster Display session 3
Resources:
Abstract
3725 - Intratumoral and peripheral exploratory biomarker analysis in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) treated with RM-1929 photoimmunotherapy
Presenter: Jack Bui
Session: Poster Display session 3
Resources:
Abstract
2533 - A nomogram based prognostic score to predict overall survival (OS) in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with immune checkpoint inhibitors (ICI).
Presenter: Luay Mousa
Session: Poster Display session 3
Resources:
Abstract