Whole exome sequencing facilitated diagnosis of patients with multiple mucinous neoplasms of the female genital tract.

e17513 Background: The differential diagnosis is challenging in clinical practice, especially among gastric-type AD of the cervix with ovarian metastases, multiple primary mucinous neoplasm in cervix and ovary, and synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT). Previous studies have revealed that next-generation sequencing might be a feasible tool in identifying the origin of tumor. Herein, whole exome sequencing (WES) was performed to distinguish patients with metastatic disease. Methods: WES analysis was performed on 28 tumors and 7 normal tissues derived from 8 patients. Each patient had one lesion of the cervix uteri. Most of them had lesions at other anatomical sites, including corpus uteri, ovary, oviduct, vermiform appendix and omentum. Mutations signatures and clonal evaluation inferred from single-nucleotide/copy number variants were explored. Results: Previous studies of multiple types of cancer have identified more than 40 single-base substitution (SBS) signatures. SBS3/6 referring to defective DNA mismatch repair and SBS10 reported in both uterus and colorectal AD were significantly enriched in this study. Next, we found no significant distribution of SBS3/6/10 among tumors at different anatomical sites. These findings indicate that primary cervical/ovarian AD with metastases other than multiple primary cancers was the predominant histology in 8 patients. The association of genomic alterations in POLE/ POLD1/HRR pathway with the distribution of SBS signatures was explored. SBS3 had a trend of significant distribution (p = 0.01) in four patients who had germline alterations in HRR pathway. Furthermore, SBS10 was significantly enriched (p = 0.009) in 2 patients with germline POLE/POLD1 alterations. Clonal evolution analyses revealed that 2 patients were identified as having SMMN-FGT, and other 6 patients had dominant clones in different tumors, which suggested a . Notably, besides the dominant clones and subclones, some tumors also exhibited extra independent clones, which might be the mixed histology of primary and metastatic tumor. In addition, we found the difference of overall survival in patients having gastric-type AD of the cervix with ovarian metastases and cervical AD patients with different FIGO stage disease based on SEER database data. Conclusions: Our study demonstrated that WES might be a feasible tool to distinguish patients having primary cervical AD with multiple metastases from those with multiple primary cancers of the female genital tract, which suggests that WES proved valuable in facilitating the diagnostic workup. A prospective, multi-center, large cohort study is needed to investigate the performance of WES in identifying the origin of tumors in patients with multiple tumors of the FGT.