Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival

• Published in: Scientific reports Vol. 10; no. 1; p. 1003
• Main Authors: Granados-Soler, José Luis, Bornemann-Kolatzki, Kirsten, Beck, Julia, Brenig, Bertram, Schütz, Ekkehard, Betz, Daniela, Junginger, Johannes, Hewicker-Trautwein, Marion, Murua Escobar, Hugo, Nolte, Ingo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-01-2020; Nature Publishing Group
• Subjects: 45; 45/23; 631/67/1347; 692/308/575; 692/4017; 692/4028/67/1347; Animals; Breast cancer; Cancer; Cat Diseases - genetics; Cat Diseases - mortality; Cat Diseases - pathology; Cats; Chromosomes; DNA Copy Number Variations - genetics; Female; GATA-3 protein; High-Throughput Nucleotide Sequencing - veterinary; Humanities and Social Sciences; Mammary gland; Mammary Neoplasms, Animal - genetics; Mammary Neoplasms, Animal - mortality; Mammary Neoplasms, Animal - pathology; Medical prognosis; Mesenchyme; Metastases; multidisciplinary; Multivariate analysis; Myc protein; Next-generation sequencing; Repressors; Science; Science (multidisciplinary); Surgery; Survival; Survival Analysis; Transcription factors; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-57942-7

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.