Differential copy number alteration profiles among gynecological malignancies.

Abstract

e14744 Background: Copy number alterations (CNA) constitutes a genomic hallmark that defines specific outcomes in gynecological neoplasms, as evidenced by the integrated analysis of the high-grade serous ovarian carcinoma (HGSOC) and endometrial carcinomas (EC) performed by the TCGA Consortium. The purpose of this study is to set up an NGS-based technology to obtain CNA profiles on formalin-fixed paraffin-embedded (FFPE) samples with clinical utility. Methods: FFPE blocks from 14 EC and 12 HGSOC were analyzed using a SureSelectXT custom panel plus OneSeq backbone, interrogating 147.000 SNPs (Agilent). CNA groups were defined in EC with a RF algorithm based on genotyping data as previously reported (Romero, ASCO 2018) and in HGSOC Homologous recombination deficiency (HRD) was determined by sequencing a serie of 35 HR genes. saasCNV pipeline was used to perform CNA calling. Results: Ten (38.50 %) of our cases were classified as CN Low (CNL), 8 as CN high (CNH)-RF (30.75 %) and 8 CNH-HRD (30.75 %). CNL profiles from EC and OC are homogenous in terms of genomic stability. CNH-RF and CNH-HRD cases harbor the highest percentage of genomic instability (p = 0.012) with distinct patterns of CNA. CNH-HRD is characterized by a higher ratio of genomic losses (p = 0.023). However, CNH-RF is mainly defined by gains (p = 0.011) (Table). Conclusions: Our NGS-based approach represents a FFPE clinically available procedure to define CNA alterations in gynecological cancer with distinct CNH patterns with prognostic potential.[Table: see text]