Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival.

ABSTRACT

Feline mammary carcinomas (FMCs) are highly malignant. As the disease-free survival (DFS) and overall survival (OS) are short, prognostication is crucial. Copy-number variations (CNVs) analysis by next-generation sequencing serves to identify critical cancer-related genomic regions. Thirty-three female cats with FMCs were followed during two years after surgery. Tumours represented tubulopapillary and solid carcinomas encompassing six molecular subtypes. Regardless of the histopathological diagnosis, molecular subtypes showed important differences in survival. Luminal A tumours exhibited the highest DFS (p = 0.002) and cancer-specific OS (p = 0.001), and the lowest amount of CNVs (p = 0.0001). In contrast, basal-like triple-negative FMCs had the worst outcome (DFS, p < 0.0001; and OS, p < 0.00001) and were the most aberrant (p = 0.05). In the multivariate analysis, copy-number losses (CNLs) in chromosome B1 (1-23 Mb) harbouring several tumour-repressors (e.g. CSMD1, MTUS1, MSR1, DBC2, and TUSC3) negatively influenced DFS. Whereas, copy-number gains (CNGs) in B4 (1-29 Mb) and F2 (64-82.3 Mb) comprising epithelial to mesenchymal transition genes and metastasis-promoting transcription factors (e.g. GATA3, VIM, ZEB1, and MYC) negatively influenced DFS and cancer-specific OS. These data evidence an association between specific CNVs in chromosomes B1, B4 and F2, and poor prognosis in FMCs.