The over-all 5-methylcytosine (m5C) content of DNA from normal tissues varies considerably in a tissue-specific manner. By high-performance liquid chromatography, we have examined the m5C contents of enzymatic digests of DNA from 103 human tumors including benign, primary malignant and secondary malignant neoplasms. The diversity and large number of these tumor samples allowed us to compare the range of DNA methylation levels from neoplastic tissues to that of normal tissues from humans. Most of the metastatic neoplasms had significantly lower genomic m5C contents than did most of the benign neoplasms or normal tissues. The percentage of primary malignancies with hypomethylated DNA was intermediate between those of metastases and benign neoplasms. These findings might reflect an involvement of extensive demethylation of DNA in tumor progression. Such demethylation could be a source of the continually generated cellular diversity associated with cancer.

The influence of selective breeding on the incidence of cutaneous melanomas was studied in the Sinclair miniature swine melanoma model. Evaluation of the results of a large breeding study that produced 349 live progeny indicated that the incidence of melanomas (54%) was highest i n newborn progeny derived from melanoma female x melanoma male (MFX MM) matings. Newborn progeny f r o m normal female x melanoma male ( N F x MM) and melanoma female x normal male ( M F x N M ) matings had incidences of 22% and 21% respectively; normal female x normal male ( N F x N M ) progeny had an incidence of 2%.Although most of the progeny were black, melanomas were observed i n swine of various colors. Tumors occurred a t differing cutaneous sites and did not demonstrate a predilection for any particular area of the body. During the f i r s t year of life, additional melanomas developed i n some animals from all groups of progeny. A t 1 year of age, the incidence of melanomas (85%) remained highest in M F x M M progeny. The incidence had increased t o 57% and 50% i n progeny from N F x M M and M F x NM matings while N F x NM progeny had an incidence of 4%. Although tumors were observed i n newborn swine, most of the tumors (75.5%) developed after birth either f r o m flat melanocytic lesions (19.3%) o r f r o m skin free of detectable melanocytic lesions (80.7%). An age effect was observed i n tumor development; tumor development decreased as the age of the animals increased. These results demonstrate that selective breeding influences the incidence of melanomas i n Sinclair swine and provide basic information required for further studies of tumor development, growth and regression in this unique spontaneous tumor system.The Sinclair miniature swine melanoma model system displays a vast array of pigmentary abnormalities, including cutaneous melanomas. Early studies with this model indicated that melanocytic tumors developed spontaneously in these swine, grew progressively, and demonstrated a high incidence of spontaneous regression (Hook et al., 1977;Millikan et al., 1973 Millikan et al., , 1974. This model was seen to provide a unique opportunity to study important aspects of tumor development, growthand regression.The Sinclair swine melanoma was first observed in 1967 (Strafuss et al., 1968) in one animal of the Sinclair miniature swine breeding herd. Strafuss et al. (1968) examined 100 swine of unstated ages from this herd and estimated the incidence of cutaneous melanocytic lesions at 21 %. The melanocytic lesions initially were divided into two types: an exophytic " nevus-like melanoma " present in 11 % and a pigmented, flat lentigo-like spot present in 15% of the animals (Strafuss et al., 1968; Flat et a/., 1968). A limited breeding experiment initiated to investigate the effect of selective breeding o n the incidence of cutaneous exophytic melanomas indicated that the incidence of this tumor was 62 % in newborn offspring of affected parents (Millikan et al., 1974).These studies, pzrfornied with a limited numbzr of aqima...

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Two cases of ciliated endometrial adenocarcinoma which came to attention in less than one year are described. This entity deserves emphasis, as its ciliation may distract from its histological malignant features. Association of cilia with atypical nuclear features in the same cell is the diagnostic characteristic which distinguishes it from non-ciliated adenocarcinoma overrunning non-malignant ciliated endometrium. The ultrastructural detail of the cilia of malignant cells does not differ from that of non-malignant endometrial glandular epithelium. Our cases raise the question of a possible association of estrogenic effect with ciliated endometrial adenocarcinoma.