Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer

Cancers
Jin WangShaying Zhao

Abstract

Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E. Invasive canine tumors harbor prominent fibroblast proliferation and overactivated stroma. Both groups have recurrent TP53 mutations. We observed three invasion patterns in canine tumors: collective, crypt-like and epithelial⁻mesenchymal transition (EMT). We detected enriched Helicobacter bilis and Alistipes finegoldii in proliferative and crypt-like tumors, but depleted mucosa-microbes in the EMT tumor. Second, guided by our canine findings, we classified 79% of 478 human colon cancers from The Cancer Genome Atlas into four subtypes: primarily proliferative, or with collective, crypt-like or EMT invasion features. Their molecular characteristics match those of canine tumors. We showed that consensus molecular subtype 4 (mesenchymal) of human CRC should be further divided into EMT an...Continue Reading

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Citations

Jul 6, 2019·Frontiers in Aging Neuroscience·Yoko M AmbrosiniJonathan P Mochel
Sep 6, 2019·Helicobacter·Armelle Ménard, Annemieke Smet
Jun 22, 2021·Critical Reviews in Microbiology·Sofia Ochoa, Luis Collado
Aug 5, 2021·Nature Communications·Burair A AlsaihatiShaying Zhao

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Datasets Mentioned

BETA
PRJNA418842

Methods Mentioned

BETA
xenograft
RNA-seq
Whole Genome Sequencing
ubiquitination
Illumina sequencing

Software Mentioned

MuTect
BWA
GATK
ssGSEA

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