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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

Phylogenetic analysis of human breast tumor MMTV-like LTR sequences showing that the human and mouse sequences do not cluster as two distinct species. The 12 human MMTV-like LTR sequences from the three family members as well as the human sequences previously isolated from human breast tumors, non-Hodgkin's lymphomas, and primary biliary cirrhosis tissue, clustered with their murine counterparts. Boxes denote LTR sequences from mother (M-S1-4), daughter (D-S1-4), and father (F-S1-4). Previously published human isolates AF346815, AY325271, AF243039, AY652977, AY652968, AY652964, AY652975, AY652974, AY652967, AY652969, AY652973, from human breast tumors [6,16,27], AY652970, AY652976, AY652978, AY652965, AY652971, AY652966, AY652972 from human non-Hodgkin's lymphomas [6], and AF513913, AF513923, from human primary biliary cirrhosis patients [26,27]. The mouse sequences, JYG, FM, and SW21 from Asian mice that were used to root the tree, the endogenous MMTV proviral sequences Mtv-8, Mtv-1, and Mtv-6, and the exogenous MMTV sequences BR6, HEJ, and C3H are bolded. Numbers on branches indicate percent frequencies of assortment in an individual branch after the bootstrap procedure (45) and indicate the robustness of branch assignments. Branch lengths are indicative of the number of nucleotide changes to individual branch points (see scale bar).
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Figure 5: Phylogenetic analysis of human breast tumor MMTV-like LTR sequences showing that the human and mouse sequences do not cluster as two distinct species. The 12 human MMTV-like LTR sequences from the three family members as well as the human sequences previously isolated from human breast tumors, non-Hodgkin's lymphomas, and primary biliary cirrhosis tissue, clustered with their murine counterparts. Boxes denote LTR sequences from mother (M-S1-4), daughter (D-S1-4), and father (F-S1-4). Previously published human isolates AF346815, AY325271, AF243039, AY652977, AY652968, AY652964, AY652975, AY652974, AY652967, AY652969, AY652973, from human breast tumors [6,16,27], AY652970, AY652976, AY652978, AY652965, AY652971, AY652966, AY652972 from human non-Hodgkin's lymphomas [6], and AF513913, AF513923, from human primary biliary cirrhosis patients [26,27]. The mouse sequences, JYG, FM, and SW21 from Asian mice that were used to root the tree, the endogenous MMTV proviral sequences Mtv-8, Mtv-1, and Mtv-6, and the exogenous MMTV sequences BR6, HEJ, and C3H are bolded. Numbers on branches indicate percent frequencies of assortment in an individual branch after the bootstrap procedure (45) and indicate the robustness of branch assignments. Branch lengths are indicative of the number of nucleotide changes to individual branch points (see scale bar).

Mentions: To analyze relationships between viral strains, phylogenetic trees have been constructed on the basis of alignments of LTR ORF sequences [24]. Phylogenetic analysis of the entire 630 bp LTR ORF sequences isolated from each of the three family members diagnosed with breast cancer is shown in Figure 5. All 12 of the human MMTV-like LTR ORF sag clones segregated to two branches of the MMTV phylogenetic tree, Mtv-8 [20,21] and Mtv-1 [22,23], and did not form a branch of their own. Moreover, clones isolated from the same family member segregated to these two separate branches. Interestingly, all of the prior MMTV-like LTR isolates from breast cancer [6,16,25], non-Hodgkin's lymphoma [5], and primary biliary cirrhosis [26,27] patients also associated with these two branches of the MMTV phylogenetic tree.


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)

Phylogenetic analysis of human breast tumor MMTV-like LTR sequences showing that the human and mouse sequences do not cluster as two distinct species. The 12 human MMTV-like LTR sequences from the three family members as well as the human sequences previously isolated from human breast tumors, non-Hodgkin's lymphomas, and primary biliary cirrhosis tissue, clustered with their murine counterparts. Boxes denote LTR sequences from mother (M-S1-4), daughter (D-S1-4), and father (F-S1-4). Previously published human isolates AF346815, AY325271, AF243039, AY652977, AY652968, AY652964, AY652975, AY652974, AY652967, AY652969, AY652973, from human breast tumors [6,16,27], AY652970, AY652976, AY652978, AY652965, AY652971, AY652966, AY652972 from human non-Hodgkin's lymphomas [6], and AF513913, AF513923, from human primary biliary cirrhosis patients [26,27]. The mouse sequences, JYG, FM, and SW21 from Asian mice that were used to root the tree, the endogenous MMTV proviral sequences Mtv-8, Mtv-1, and Mtv-6, and the exogenous MMTV sequences BR6, HEJ, and C3H are bolded. Numbers on branches indicate percent frequencies of assortment in an individual branch after the bootstrap procedure (45) and indicate the robustness of branch assignments. Branch lengths are indicative of the number of nucleotide changes to individual branch points (see scale bar).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Phylogenetic analysis of human breast tumor MMTV-like LTR sequences showing that the human and mouse sequences do not cluster as two distinct species. The 12 human MMTV-like LTR sequences from the three family members as well as the human sequences previously isolated from human breast tumors, non-Hodgkin's lymphomas, and primary biliary cirrhosis tissue, clustered with their murine counterparts. Boxes denote LTR sequences from mother (M-S1-4), daughter (D-S1-4), and father (F-S1-4). Previously published human isolates AF346815, AY325271, AF243039, AY652977, AY652968, AY652964, AY652975, AY652974, AY652967, AY652969, AY652973, from human breast tumors [6,16,27], AY652970, AY652976, AY652978, AY652965, AY652971, AY652966, AY652972 from human non-Hodgkin's lymphomas [6], and AF513913, AF513923, from human primary biliary cirrhosis patients [26,27]. The mouse sequences, JYG, FM, and SW21 from Asian mice that were used to root the tree, the endogenous MMTV proviral sequences Mtv-8, Mtv-1, and Mtv-6, and the exogenous MMTV sequences BR6, HEJ, and C3H are bolded. Numbers on branches indicate percent frequencies of assortment in an individual branch after the bootstrap procedure (45) and indicate the robustness of branch assignments. Branch lengths are indicative of the number of nucleotide changes to individual branch points (see scale bar).
Mentions: To analyze relationships between viral strains, phylogenetic trees have been constructed on the basis of alignments of LTR ORF sequences [24]. Phylogenetic analysis of the entire 630 bp LTR ORF sequences isolated from each of the three family members diagnosed with breast cancer is shown in Figure 5. All 12 of the human MMTV-like LTR ORF sag clones segregated to two branches of the MMTV phylogenetic tree, Mtv-8 [20,21] and Mtv-1 [22,23], and did not form a branch of their own. Moreover, clones isolated from the same family member segregated to these two separate branches. Interestingly, all of the prior MMTV-like LTR isolates from breast cancer [6,16,25], non-Hodgkin's lymphoma [5], and primary biliary cirrhosis [26,27] patients also associated with these two branches of the MMTV phylogenetic tree.

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