Cross-species oncogenic signatures of breast cancer in canine mammary tumors.

Nature Communications
Tae-Min KimSangwoo Kim

Abstract

Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs.

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Citations

Dec 31, 2020·Animals : an Open Access Journal From MDPI·Ying ZhaoDegui Lin
Feb 15, 2021·Seminars in Cancer Biology·Stefan WernerKlaus Pantel
Mar 4, 2021·Animals : an Open Access Journal From MDPI·Cristian G TorresPamela Cruz
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Aug 8, 2021·Animals : an Open Access Journal From MDPI·Soo-Hyeon KimJung-Hyang Sur
Aug 23, 2021·Translational Oncology·Hester A DoyleMark J Mamula
Oct 30, 2021·Frontiers in Veterinary Science·Chen MeiYanli Lyu

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Datasets Mentioned

BETA
GSE31519

Methods Mentioned

BETA
RNA-seq
deamination
xenograft
PCR

Software Mentioned

TopHat
R
BWA
ESTIMATE
ESTIMATE R
Crossmap
blastz
SAMTOOLS
Cufflinks
Ensembl

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