Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype.
Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer.
SRI International, Biosciences Division, 333 Ravenswood Ave, Menlo Park, CA, USA.
Gary L
GL
Johanning
Department of Medical Oncology, Groupe Hospitalier Pitié-Salpêtrière, Université Pierre and Marie Curie (Paris VI), GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Assistance-Publique Hôpitaux de Paris, Paris, France.
Gabriel G
GG
Malouf
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiaofeng
X
Zheng
Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
Francisco J
FJ
Esteva
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John N
JN
Weinstein
SRI International, Biosciences Division, 333 Ravenswood Ave, Menlo Park, CA, USA.
Feng
F
Wang-Johanning
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiaoping
X
Su
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology*; D016208:Databases, Factual; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D015894:Genome, Human; D006801:Humans; D014759:Viral Envelope Proteins / Q000235:genetics*
D014759:Viral Envelope Proteins