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Mouse mammary tumor virus (MMTV)-like DNA sequences in the breast tumors of father, mother, and daughter.

Etkind PR, Stewart AF, Wiernik PH - Infect. Agents Cancer (2008)

Bottom Line: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members.The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent.

View Article: PubMed Central - HTML - PubMed

Affiliation: Our Lady of Mercy Medical Center-Comprehensive Cancer Center, New York Medical College, Bronx, New York, USA. petkind@olmhs.org

ABSTRACT

Background: The diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. Both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (MMTV), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. The aim of this study was to determine if MMTV might be involved in the breast cancer of this cluster of three family members.

Results: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members. The amplified env gene sequences were 98.0%-99.6% homologous to the MMTV env sequences found in the GR, C3H, and BR6 mouse strains. The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.

Conclusion: The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent. Phylogenetic data suggest that the MMTV-like DNA sequences are mouse and not human derived and that the ultimate reservoir of MMTV is most likely the mouse. Although the route by which these family members came to be infected with MMTV is unknown, the possibility exists that such infection may have resulted from a shared exposure to mice.

No MeSH data available.


Related in: MedlinePlus

Hematoxylin and eosin stained slides of formalin-fixed, paraffin-embedded tissue sample blocks of breast tumor tissue and metastatic breast tumor tissue in lymph node. Panel A (father): metastatic ductal carcinoma of breast in axillary lymph node. The tumor is almost completely replacing the normal tissue in this 2-cm node. Note the rim of residual subcapsular lymphoid tissue. Panel B (mother): invasive moderately differentiated ductal carcinoma of breast. Note the prominent lymphocytic response. Panel C (daughter): invasive and in situ lobular carcinoma of breast. Only a portion of the round edge of a lobule containing lobular carcinoma in situ is seen here. Magnification is 200X.
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Figure 1: Hematoxylin and eosin stained slides of formalin-fixed, paraffin-embedded tissue sample blocks of breast tumor tissue and metastatic breast tumor tissue in lymph node. Panel A (father): metastatic ductal carcinoma of breast in axillary lymph node. The tumor is almost completely replacing the normal tissue in this 2-cm node. Note the rim of residual subcapsular lymphoid tissue. Panel B (mother): invasive moderately differentiated ductal carcinoma of breast. Note the prominent lymphocytic response. Panel C (daughter): invasive and in situ lobular carcinoma of breast. Only a portion of the round edge of a lobule containing lobular carcinoma in situ is seen here. Magnification is 200X.

Mentions: Three members of the same family, father, mother, and daughter, were diagnosed with carcinoma of the breast with axillary nodal metastases. The father was the first to be diagnosed at the age of 79 in 1963. The mother and daughter were each diagnosed six years later in 1969 at the ages of 82 and 56 respectively. All three family members had invasive carcinoma as shown in Figure 1. Published data from five laboratories including our own have shown an association of the betaretrovirus mouse mammary tumor virus (MMTV) with a certain percentage of human breast tumors [1-5]. In addition we identified MMTV-like DNA sequences in both breast tumor tissue and non-Hodgkin's lymphoma tissue of eight patients diagnosed with both diseases and in the lymphoma tissue of three patients diagnosed with only non-Hodgkin's lymphoma [6]. We and others have not detected MMTV in normal human tissue [1,6,7]. In mice MMTV is the etiological agent responsible for the development of breast tumors as well as certain B-and T-cell lymphomas [8-10]. In this study we investigated the presence of MMTV-like DNA sequences in three family members each of whom had been diagnosed with breast cancer. We have detected the presence of both the MMTV-like envelope (env) and long terminal repeat (LTR) gene sequences in all three patients.


Mouse mammary tumor virus (MMTV)-like DNA sequences in the breast tumors of father, mother, and daughter.

Etkind PR, Stewart AF, Wiernik PH - Infect. Agents Cancer (2008)

Hematoxylin and eosin stained slides of formalin-fixed, paraffin-embedded tissue sample blocks of breast tumor tissue and metastatic breast tumor tissue in lymph node. Panel A (father): metastatic ductal carcinoma of breast in axillary lymph node. The tumor is almost completely replacing the normal tissue in this 2-cm node. Note the rim of residual subcapsular lymphoid tissue. Panel B (mother): invasive moderately differentiated ductal carcinoma of breast. Note the prominent lymphocytic response. Panel C (daughter): invasive and in situ lobular carcinoma of breast. Only a portion of the round edge of a lobule containing lobular carcinoma in situ is seen here. Magnification is 200X.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2277433&req=5

Figure 1: Hematoxylin and eosin stained slides of formalin-fixed, paraffin-embedded tissue sample blocks of breast tumor tissue and metastatic breast tumor tissue in lymph node. Panel A (father): metastatic ductal carcinoma of breast in axillary lymph node. The tumor is almost completely replacing the normal tissue in this 2-cm node. Note the rim of residual subcapsular lymphoid tissue. Panel B (mother): invasive moderately differentiated ductal carcinoma of breast. Note the prominent lymphocytic response. Panel C (daughter): invasive and in situ lobular carcinoma of breast. Only a portion of the round edge of a lobule containing lobular carcinoma in situ is seen here. Magnification is 200X.
Mentions: Three members of the same family, father, mother, and daughter, were diagnosed with carcinoma of the breast with axillary nodal metastases. The father was the first to be diagnosed at the age of 79 in 1963. The mother and daughter were each diagnosed six years later in 1969 at the ages of 82 and 56 respectively. All three family members had invasive carcinoma as shown in Figure 1. Published data from five laboratories including our own have shown an association of the betaretrovirus mouse mammary tumor virus (MMTV) with a certain percentage of human breast tumors [1-5]. In addition we identified MMTV-like DNA sequences in both breast tumor tissue and non-Hodgkin's lymphoma tissue of eight patients diagnosed with both diseases and in the lymphoma tissue of three patients diagnosed with only non-Hodgkin's lymphoma [6]. We and others have not detected MMTV in normal human tissue [1,6,7]. In mice MMTV is the etiological agent responsible for the development of breast tumors as well as certain B-and T-cell lymphomas [8-10]. In this study we investigated the presence of MMTV-like DNA sequences in three family members each of whom had been diagnosed with breast cancer. We have detected the presence of both the MMTV-like envelope (env) and long terminal repeat (LTR) gene sequences in all three patients.

Bottom Line: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members.The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent.

View Article: PubMed Central - HTML - PubMed

Affiliation: Our Lady of Mercy Medical Center-Comprehensive Cancer Center, New York Medical College, Bronx, New York, USA. petkind@olmhs.org

ABSTRACT

Background: The diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. Both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (MMTV), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. The aim of this study was to determine if MMTV might be involved in the breast cancer of this cluster of three family members.

Results: MMTV-like envelope (env) and long terminal repeat (LTR) sequences containing the MMTV superantigen gene (sag) were detected in the malignant tissues of all three family members. The amplified env gene sequences were 98.0%-99.6% homologous to the MMTV env sequences found in the GR, C3H, and BR6 mouse strains. The amplified LTR sequences containing sag sequences segregated to specific branches of the MMTV phylogenetic tree and did not form a distinct branch of their own.

Conclusion: The presence of MMTV-like DNA sequences in the malignant tissues of all three family members suggests the possibility of MMTV as an etiological agent. Phylogenetic data suggest that the MMTV-like DNA sequences are mouse and not human derived and that the ultimate reservoir of MMTV is most likely the mouse. Although the route by which these family members came to be infected with MMTV is unknown, the possibility exists that such infection may have resulted from a shared exposure to mice.

No MeSH data available.


Related in: MedlinePlus