Abstract 1119P
Background
Neuroendocrine carcinomas (NECs) are rare, but aggressive malignant tumors of female genital tract, especially in uterine the cervix.
Methods
Aiming to explore the genomic alteration characteristics of female genital tract NECs, 9 cases were enrolled, including 6 uterine NECs, 2 cervix NECs and 1 ovary NEC. Targeted next generation sequencing (NGS) of 450 genes was performed in a CAP/CLIA certified OrigiMed laboratory (Shanghai, China). Genomic alterations, tumor mutational burden (TMB), PD-L1 expression and microsatellite status were analyzed. Subsequently, potential target drugs and immune checkpoint inhibitors (ICIs) were assessed.
Results
The median TMB value was 3.1 (0.5-20.1) muts/Mb, and only 1 patient, large cell uterine NECs, was TMB-H (20.1 muts/Mb). All of them were MSS and PD-L1 negative. It suggested that most of them might be not benefit from immune checkpoint inhibitors (ICIs). In all NECs, 33.33% (3/9) were I stage, 33.33% (3/9) III-IV stage, and others unknown. The top 8 most-frequently aberrant genes were ARID1A (33.33%, 3/9), PTEN (33.33%, 3/9), ATRX (22.22%, 2/9), KMT2C (22.22%, 2/9), KMT2D (22.22%, 2/9), NOTCH2 (22.22%, 2/9), SMARCA4 (22.22%, 2/9) and TP53 (22.22%, 2/9). Moreover, 4 (44.44%) patients were with at least one drugable alteration, and 3 of them were large cell uterine NECs and one ovary NEC. Interestingly, all large cell uterine NECs had potential targets (n=3), and on the contrary, all small cell uterine NECs had no potential targets (n=2). Among them, 3 cases with PIK3CA or PTEN mutations recommended with PI3K/mTOR inhibitors, and further, one of them co-mutated with CDKN2A and CDKN2B, which might also be benefit from CDK4/6 inhibitors. The remaining patient with target drug recommendation had two single nucleotide variants (SNV) ATM p. D1682Y and FGFR2 p.S252W, which indicated potential effectiveness to PAPR inhibitor and FGFR inhibitor.
Conclusions
Our study firstly revealed the characteristics of gene variations, biomarkers and potential target drugs in Chinese NEC patients originated from female genital tract.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.