Mouse mammary tumor virus (MMTV) - like exogenous sequences are associated with sporadic but not hereditary human breast carcinoma

Aging (Albany NY). 2019 Sep 13;11(17):7236-7241. doi: 10.18632/aging.102252. Epub 2019 Sep 13.


The inheritance of mutated suppressor genes, such as BRCA1 and BRCA2, is acknowledged as an etiological factor in hereditary breast carcinoma (HBC). Two different molecular mechanisms are possible; the Knudson's "two hits" or the gene haploinsufficiency. Etiology of sporadic breast carcinoma (SBC) is not known, although data support the possible role of the betaretrovirus Mouse Mammary Tumor Virus (MMTV). This study analyzes the presence of MMTV exogenous sequences in two representative groups of HBC and SBC, excluding any contamination by murine and retroviral material and endogenous betaretroviruses. The 30.3% of 56 SBC contained MMTV sequences, against the 4.2% of 47 HBC (p < 0.001). Cases positive for viral sequences showed the presence of p14, signal peptide of the MMTV envelope precursor. This result was expected based on the fact that HBCs, having a specific genetic etiology, do not need the action of a carcinogenetic viral agent. Moreover, the striking results obtained by comparing two groups of vastly different tumors represent an additional element of quality control: the distinction between HBC and SBC is so well-defined that results cannot be ascribed to mere coincidence. This paper strengthens the hypothesis for a viral etiology for human sporadic breast carcinoma.

Keywords: HMTV; MMTV; breast cancer etiology; hereditary breast cancer; sporadic breast cancer; viral cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / virology*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / virology*
  • Genes, BRCA1
  • Genes, BRCA2
  • Genes, Tumor Suppressor
  • Germ-Line Mutation
  • Humans
  • Mammary Tumor Virus, Mouse / genetics*
  • Middle Aged
  • Oncogene Proteins / metabolism


  • CDK2AP2 protein, human
  • Oncogene Proteins