Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity.
Science
; 384(6699): eadh8697, 2024 May 31.
Article
in En
| MEDLINE
| ID: mdl-38815010
ABSTRACT
Tumors with the same diagnosis can have different molecular profiles and response to treatment. It remains unclear when and why these differences arise. Somatic genomic aberrations occur within the context of a highly variable germline genome. Interrogating 5870 breast cancer lesions, we demonstrated that germline-derived epitopes in recurrently amplified genes influence somatic evolution by mediating immunoediting. Individuals with a high germline-epitope burden in human epidermal growth factor receptor 2 (HER2/ERBB2) are less likely to develop HER2-positive breast cancer compared with other subtypes. The same holds true for recurrent amplicons defining three aggressive estrogen receptor (ER)-positive subgroups. Tumors that overcome such immune-mediated negative selection are more aggressive and demonstrate an "immune cold" phenotype. These data show that the germline genome plays a role in dictating somatic evolution.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Germ-Line Mutation
/
Receptor, ErbB-2
/
Clonal Evolution
Limits:
Female
/
Humans
Language:
En
Journal:
Science
Year:
2024
Document type:
Article
Affiliation country:
United States