Genomics of rare gynecologic neuroendocrine carcinoma

High-grade neuroendocrine carcinomas (NECs) of the cervix are rare, aggressive cancers accounting for about 1-1.5% of all cervical cancer. The 5-year survival is up to 36% for early-stage disease; however, the advanced-stage disease has <10% survival, with relapse rates exceeding 90%. These cancers are likely to have a vascular invasion and nodal or visceral metastasis. Unfortunately, the NEC of the cervix affects young women with a median age of 37. High-grade NECs of other gynecologic origins are even rarer, share similar aggressive behavior and poor outcomes. We performed whole-exome sequencing of 14 samples. Sites of origin for tumors in our cohort were the cervix (69%), ovary (19%), and endometrium (12%). The median number of prior lines of therapy was 1. Median PFS and OS were 1 and 12 months, respectively, indicating their highly lethal nature. The WES analyses detected mutations in KMT2C, KNL1, and NCOR2 genes in all the tumor samples (100%). Our cohort demonstrated the highest TMB compared to several TCGA cohorts. The unique mutational landscape of gynecologic neuroendocrine carcinoma suggests novel multi-modality therapeutic measures to address this highly fatal cancer.