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.
OBJECTIVE
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.


METHODS
DNA was extracted from formalin-fixed, 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 non-Hodgkin'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.
Etkind
Polly R
PR
Our Lady of Mercy Medical Center-Comprehensive Cancer Center, New York Medical College, Bronx, New York, USA.
Stewart
Alexandre F R
AF
Dorai
Thambi
T
Purcell
Daniel J
DJ
Wiernik
Peter H
PH
D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000150:complications / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D015752:Genes, env / Q000235:genetics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000302:isolation & purification*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D018089:Superantigens / Q000235:genetics; D020079:Terminal Repeat Sequences
D000956:Antigens, Viral; D004279:DNA, Viral; C468299:GR protein, mouse mammary tumor virus; D018089:Superantigens