Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: Further definition of the HML-6 group

Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman w ho also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is rep orted here. It was 99% identical to HML-6.2BC1 and gave the same restrictio n fragments as total DNA. HML-6.28 is a 4.7-kb provirus with a 5'LTR, trunc ated in RT. Data from two similar genomic clones and sequences found in Gen Bank are also reported. Overlaps between them gave a rather complete pictur e of the HML-6.2BC1-like human endogenous retroviral elements. Work with so matic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, c lose to the MHC region. The causal role of HML-6.28 in breast cancer remain s unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the def inition of common and unique features of type A, B, and D (ABD) retroviruse s. In Gag, HML-6; has no intervening sequences between matrix and capsid pr oteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but g ave a phylogenetic tree different from trees made from other ABD genes, ind icating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function. (C) 1999 Academic Press.