Human breast cancer and lymphomas may share a common aetiology involving Mouse Mammary Tumour Virus (MMTV)

Cotterchio, Michelle; Nadalin, Victoria; Sauer, M K

doi:10.1016/s0306-9877(02)00204-9

Cited by 16 publications

(17 citation statements)

References 13 publications

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“…This statistically significant increased incidence of nonHodgkin's lymphoma in breast cancer patients suggests a relationship between the development of these two malignancies that is not related to therapy for either neoplasm. Numerous additional studies have also reported the occurrence of breast cancer and lymphoma in the same patient and have suggested a common link between breast cancer and non-Hodgkin's lymphoma (2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Etkind

Stewart

Dorai

et al. 2004

Clinical Cancer Research

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Purpose: In a previous study, we had detected the presence of mouse mammary tumor virus (MMTV)-like envelope (ENV) gene sequences in both the breast tumors and non-Hodgkin's lymphoma tissue of two of our breast tumor patients who had been diagnosed simultaneously with both malignancies. The aim of this study was to determine if MMTV-like DNA sequences are present in the breast tumors and non-Hodgkin's lymphomas of additional patients suffering from both malignancies and if so to characterize these sequences in detail.Experimental Design: DNA was extracted from formalinfixed, paraffin-embedded tissue sample blocks of breast tumors and non-Hodgkin's lymphomas from patients suffering from both malignancies. A 250-bp region of the MMTV ENV gene and a 630-bp region of the MMTV long terminal repeat (LTR) open reading frame (ORF) that encodes the MMTV superantigen (sag) gene were amplified by PCR from the isolated DNA. Amplified products were analyzed by Southern blotting, cloned, and sequenced.Results: MMTV-like ENV and LTR sequences were detected in both the breast tumors and non-Hodgkin's lymphomas of 6 of 12 patients suffering from both malignancies. A novel mutant of the MMTV ENV gene was identified in these patients. Characterization of the MMTV-like LTR highly variable sag sequences revealed total or nearly total identity to three distinct MMTV proviruses from two different branches of the MMTV phylogenetic tree.Conclusions: The presence of MMTV-like ENV and LTR sequences in both the breast tumors and nonHodgkin's lymphomas of 6 additional patients suggests a possible involvement of these sequences in these two malignancies. MMTV-like LTR sequence homology to different MMTV proviruses revealed the presence of more than one strain of MMTV-like sequences in each individual suggesting the possibility of multiple infections in these patients.

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Section: Introductionmentioning

confidence: 99%

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Etkind

Stewart

Dorai

et al. 2004

Clinical Cancer Research

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“…Futhermore, tolerant diseases showed a higher tendency to share functions with other pathophenotypes. Such common features at the functional level might be useful for understanding the etiology of complex genetic disorders [25]. We have presented a way of systematically assessing the prioritization tolerance of pathophenotypes emerging from the underlying protein-interaction network.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the Robustness of Network-Based Disease-Gene Prioritization Methods Reveals Redundancy in the Human Interactome and Functional Diversity of Disease-Genes

Güney

Oliva

2014

PLoS ONE

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Complex biological systems usually pose a trade-off between robustness and fragility where a small number of perturbations can substantially disrupt the system. Although biological systems are robust against changes in many external and internal conditions, even a single mutation can perturb the system substantially, giving rise to a pathophenotype. Recent advances in identifying and analyzing the sequential variations beneath human disorders help to comprehend a systemic view of the mechanisms underlying various disease phenotypes. Network-based disease-gene prioritization methods rank the relevance of genes in a disease under the hypothesis that genes whose proteins interact with each other tend to exhibit similar phenotypes. In this study, we have tested the robustness of several network-based disease-gene prioritization methods with respect to the perturbations of the system using various disease phenotypes from the Online Mendelian Inheritance in Man database. These perturbations have been introduced either in the protein-protein interaction network or in the set of known disease-gene associations. As the network-based disease-gene prioritization methods are based on the connectivity between known disease-gene associations, we have further used these methods to categorize the pathophenotypes with respect to the recoverability of hidden disease-genes. Our results have suggested that, in general, disease-genes are connected through multiple paths in the human interactome. Moreover, even when these paths are disturbed, network-based prioritization can reveal hidden disease-gene associations in some pathophenotypes such as breast cancer, cardiomyopathy, diabetes, leukemia, parkinson disease and obesity to a greater extend compared to the rest of the pathophenotypes tested in this study. Gene Ontology (GO) analysis highlighted the role of functional diversity for such diseases.

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“…This indicates that despite the lack of association between the virus and hormone receptors in the human liver, other factors could be involved in the transcription of MMTV-like virus in the human liver [Groner et al, 1985]. (iv) MMTV-like virus has been detected in hormonally influenced tumors of the breast [Wang et al, 1995[Wang et al, , 2001a[Wang et al, , 2003Etkind et al, 2000;Cotterchio et al, 2002;Ford et al, 2003Ford et al, , 2004bFaedo et al, 2004;Lawson et al, 2004]. In this study, unequivocal evidence of MMTV-like viral env gene sequences in other tumors that are hormonal influenced (ovary, prostate, endometrium, and to a certain extent skin tumors) but not in tumors of the lung with no apparent hormonal influence, as indicated by our immunohistochemistry analyses, was shown.…”

Section: Discussionmentioning

confidence: 99%

“…In rare cases MMTV induces tumors other than breast cancer, predominantly haematological malignancies of lymphocytes [Hsu et al, 1988;Yanagawa et al, 1993]. The MMTV-like virus env has previously been detected in human lymphomas [Cotterchio et al, 2002;Etkind et al, 2004] and identified recently in hepatocellular carcinomas and various liver diseases [Johal et al, 2009]. This indicates that like in the mice, MMTV-like virus in humans can also be found in organs, other than the breast.…”

Section: Introductionmentioning

confidence: 99%

DNA of mouse mammary tumor virus‐like virus is present in human tumors influenced by hormones

Johal

Faedo

Faltas

et al. 2010

Journal of Medical Virology

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Mouse mammary tumor virus (MMTV) is a hormonally regulated, oncogenic virus of mice. MMTV-like virus DNA has previously been detected in human breast cancers, liver disease, and liver cancers. It is hypothesized that local hormonal effects might be of primary importance in determining MMTV-like virus detection in human tumors. MMTV-like virus envelope (env) DNA was determined using nested PCR in 89 ovarian, 147 prostate, 50 endometrial, 141 skin, and 51 lung cancers. Viral-positive sequences were compared with published MMTV-like viral sequences from human breast cancer, liver cancer and MMTV. Immunohistochemistry for estrogen receptor (ER-alpha) and progesterone receptor (PgR) was performed on a subset of tumors. MMTV-like virus env DNA was detected in ovarian cancers (14/89; 16%), prostate cancers (53/147; 36%), endometrial cancers (5/50; 10%), skin cancers (13/141; 9%) but not in lung cancers (0/51). Phylogenetic analysis of the viral-positive sequences showed no clustering of the isolates according to tissue type. A significant association was observed between the presence of hormone receptors and detection of MMTV-like virus in the human cancers screened (P = 0.01). A significant association between MMTV-like virus and PgR was noted in skin cancers (P = 0.003). Therefore, unlike the mouse model, the detection of MMTV-like env sequences in human cancers in addition to breast indicates that MMTV-like viral expression is not breast cancer-specific and may relate to hormone-dependent viral expression.

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Human breast cancer and lymphomas may share a common aetiology involving Mouse Mammary Tumour Virus (MMTV)

Cited by 16 publications

References 13 publications

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

Analysis of the Robustness of Network-Based Disease-Gene Prioritization Methods Reveals Redundancy in the Human Interactome and Functional Diversity of Disease-Genes

DNA of mouse mammary tumor virus‐like virus is present in human tumors influenced by hormones

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