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Research Paper|Volume 11, Issue 17|pp 7236—7241

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

Antonio Giuseppe Naccarato1,2, Francesca Lessi3, Katia Zavaglia4, Cristian Scatena1,2, Mohammad A. Al Hamad5, Paolo Aretini3, Michele Menicagli3, Manuela Roncella6, Matteo Ghilli6, Maria Adelaide Caligo4, Chiara Maria Mazzanti3, Generoso Bevilacqua1,7
  • 1Division of Pathology, Department of Translational Research and New Technologies in Medicine, University of Pisa, and Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy
  • 2Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy
  • 3Fondazione Pisana per la Scienza, Pisa, Italy
  • 4Division of Molecular Genetics, Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy
  • 5Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  • 6Division of Surgery, Breast Center, Pisa University Hospital, Pisa, Italy
  • 7“San Rossore” Hospital – Casa di Cura “San Rossore”, Pisa, Italy
* Equal contribution
Received: May 31, 2019Accepted: September 2, 2019Published: September 13, 2019
https://doi.org/10.18632/aging.102252

Copyright © 2019 Naccarato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.