English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Introduction  Recent studies comparing canine mammary tumors (CMTs) and human breast cancers have revealed remarkable tumor similarities, identifying shared expression profiles and acquired mutations. CMTs can also provide a model of inherited breast cancer susceptibility in humans; thus, we investigated breed-specific whole genome sequencing (WGS) data in search for novel CMT risk factors that could subsequently explain inherited breast cancer risk in humans.    Methods  WGS was carried out on five CMT-affected Gold Retrievers from a large pedigree of 18 CMT-affected dogs. Protein truncating variants (PTVs) detected in all five samples (within human orthlogs) were validated and then genotyped in the 13 remaining CMT-affected Golden Retrievers. Allele frequencies were compared to canine controls. Subsequently, human blood-derived exomes from The Cancer Genome Atlas breast cancer cases were analyzed and allele frequencies were compared to Exome Variant Server ethnic-matched controls.    Results   Carcinoembryonic Antigen-related Cell Adhesion Molecule 24  ( CEACAM24 ) c.247dupG;p.(Val83Glyfs ∗ 48) was the only validated variant and had a frequency of 66.7% amongst the 18 Golden Retrievers with CMT. This was significant compared to the European Variation Archive ( p- value 1.52 × 10 –8 ) and non-Golden Retriever American Kennel Club breeds ( p- value 2.48 × 10 –5 ). With no direct ortholog of  CEACAM24  in humans but high homology to all CEACAM gene family proteins, all human  CEACAM  genes were investigated for PTVs. A total of six and sixteen rare PTVs were identified in African and European American breast cancer cases, respectively. Single variant assessment revealed five PTVs associated with breast cancer risk. Gene-based aggregation analyses revealed that rare PTVs in  CEACAM6 ,  CEACAM7 , and  CEACAM8  are associated with European American breast cancer risk, and rare PTVs in  CEACAM7  are associated with breast cancer risk in African Americans. Ultimately, rare PTVs in the entire  CEACAM  gene family are associated with breast cancer risk in both European and African Americans with respective  p- values of 1.75 × 10 –13  and 1.87 × 10 –04 .    Conclusion  This study reports the first association of inherited  CEACAM  mutations and breast cancer risk, and potentially implicates the whole gene family in genetic risk. Precisely how these mutations contribute to breast cancer needs to be determined; especially considering our current knowledge on the role that the  CEACAM  gene family plays in tumor development, progression, and metastasis.

CEACAM Gene Family Mutations Associated With Inherited Breast Cancer Risk – A Comparative Oncology Approach to Discovery