Biology subjects

Turner-Maier, J.

Publications and source records attributed to Turner-Maier, J..

3 recordsLinked to original sources

bioRxiv2025

The shared selection landscape of dog and human cancers

Cancers in pet dogs are prevalent, progress rapidly, and closely resemble human cancers, positioning them as powerful models for precision oncology. While genetic drivers of human cancer often transcend histologic boundaries, most comparative studies have focused on matched cancer types, leaving the broader scope of genomic similarity unresolved. We performed the first exome-wide, histology-agnostic comparison of canine and human cancers, analyzing 429 dog and 14,966 human tumors across 39 types. Mutational signatures and genes under selection are widely shared between species, and cancer types are as genomically similar between species as within species, with no greater similarity within dog breeds than between breeds. Machine-learning models identify genetic features shared by dog and human tumors of different histologies, mirroring cross-histology patterns in human cancer. These findings establish dog cancer as a powerful system for genomics-informed precision oncology and support pan-cancer approaches to discover translationally relevant models beyond histologic classification.

cancer biology↗

bioRxiv2020

Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs

Sporadic angiosarcomas (ASs) are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types of cancers, but their existence and significance remain unclear in sporadic ASs. In this study, we leveraged RNA sequencing data from thirteen human ASs and 76 spontaneous canine hemangiosarcomas (HSAs) to identify fusion genes associated with spontaneous vascular malignancies. Ten novel protein-coding fusion genes, including TEX2-PECAM1 and ATP8A2-FLT1, were identified in seven of the thirteen human tumors, with two tumors showing mutations of TP53. HRAS and NRAS mutations were found in ASs without fusions or TP53 mutations. We found fifteen novel protein-coding fusion genes including MYO16-PTK2, GABRA3-FLT1, and AKT3-XPNPEP1 in eleven of the 76 canine HSAs; these fusion genes were seen exclusively in tumors of the angiogenic molecular subtype that contained recurrent mutations in TP53, PIK3CA, PIK3R1, and NRAS. In particular, fusion genes and mutations of TP53 co-occurred in tumors with higher frequency than expected by random chance, and they enriched gene signatures predicting activation of angiogenic pathways. Comparative transcriptomic analysis of human ASs and canine HSAs identified shared molecular signatures associated with activation of PI3K/AKT/mTOR pathways. Our data show that, while driver events of malignant vasoformative tumors of humans and dogs include diverse mutations and stochastic rearrangements that create novel fusion genes, convergent transcriptional programs govern the highly conserved morphological organization and biological behavior of these tumors in both species.

cancer biology↗

bioRxiv2019

Genomic analysis reveals shared genes and pathways in human and canine angiosarcoma

Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with high fatality and few effective treatment options. It is both rare and heterogenous, making large, well powered genomic studies nearly impossible. In dogs, angiosarcoma is common, with breeds like the golden retriever carrying heritable genetic factors that put them at very high risk. If the clinical similarity of canine and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine angiosarcoma via whole exome sequencing (47 golden retriever angiosarcomas) and RNA sequencing (74 angiosarcomas from multiple breeds). The predominant mutational signature was the age-associated deamination of cytosine to thymine, and somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). We compared the canine data to human data recently released by The Angiosarcoma Project, and found the same genes and many of the same pathways significantly enriched for somatic mutations, most notably protein kinases, glycoproteins, fibronectin Type III domains, EGF-like domains, and cell adhesion proteins such as cadherins. As in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. Canine angiosarcoma closely models human angiosarcoma on a genomic level, and is a powerful tool for investigating the pathogenesis of this devastating disease.

genomics↗