Identification of Integration Sites of Mouse Mammary Tumor Virus in Human Breast Cancer Tissues

Abstract

Mouse mammary tumor virus (MMTV) is an established cause of mammary tumors in mice but its role in human breast cancer is still controversial. MMTV has been detected in human breast cancer samples in several parts of the world, but the establishment of a causal role is under debate. Several groups have reported presence of MMTV-like sequences in human breast cancer. We have also identified MMTV like sequences in 26% of breast cancer tissues from Pakistani population. Here we propose that integration site analysis of MMTV might help in establishing its role in breast cancer development. We have used LM-PCR to identify integration sites of MMTV. Human DNA from Breast cancer samples was digested and ligated to linkers. An MMTV specific and a linker specific primer were used to amplify integration site. Amplified DNA was isolated by shotgun cloning in bacteria. Identification of thirteen distinct integration sites supports the idea of a viral etiology of breast cancer. Furthermore, our data also indicates anomalous behavior of MMTV-like sequences. Previous data suggests a totally random integration of MMTV in both mouse and human genome in cell lines. However we have identified 5 identical integration sites in eight different breast cancer tissue samples. One particular site at locus 3q26.2 was identified from 7 samples. This data also supports sequence specific integration of MMTV. This study is first of its kind in MMTV research. Although, the link is still not clear, but further studies on these integration sites might reveal a link between MMTV-like sequences and human breast cancer.