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Papillary serous peritoneal carcinoma (PSPC) is histologically indistinguishable from papillary serous ovarian carcinoma (PSOC) with a similar clinical presentation, yet may differ in its carcinogenesis. The purpose of this study was to determine the incidence of allelic loss and the frequency of p53 mutation by p53 overexpression in PSPC compared to PSOC.An allelotype analysis of 26 patients with PSPC was performed using 39 microsatellite markers from 25 chromosomal arms. Thirty-seven previously studied patients with PSOC served as the comparison. P53 mutations were detected by immunohistochemical protein overexpression.There was significantly less LOH in PSPC than PSOC. Both the number of chromosomes with LOH and the proportion of tumors with allelic loss were less frequent. Significant LOH, defined as/=30% of informative tumors having loss at a chromosome locus, was seen on 4 chromosome arms in PSPC: 12p, 17p, 17q, and 18q, compared to 18 arms in PSOC: 4q, 5q, 6p, 6q, 9p, 9q, 12p, 12q, 13q, 15q, 16q, 17p, 17q, 18q, 19p, 19q, 22q, and Xq (P0.001). The median LOH frequency was higher in PSOC than PSPC, 43% versus 33%, respectively (P = 0.013), and more PSOC tumors had LOH than PSPC tumors, 91% versus 65% (P = 0.042). P53 overexpression was detected in 80% of PSPC tumors.LOH occurs less frequently in PSPC compared to PSOC. Chromosomal regions with high frequencies of LOH common to PSPC and PSOC, such as 12p, 17p, 17q, and 18q, may harbor tumor suppressor genes important in the carcinogenesis of both malignancies and likely include p53.

Background Molecular genetic markers to identify the 13% lymph node-negative mammary carcinomas that are prone to develop metastases would clearly be of considerable value in indicating those cases in need of early aggressive therapy. Methods Representational difference analysis was used in an attempt to identify genetic alterations related to breast cancer metastasis by comparing genomic DNA from microdissected normal cells and from metastatic cells of ductal breast carcinoma patients. Results Representational difference analysis products yielded 10 unique metastasis-associated DNA sequences (MADS), i.e. products apparently lost in metastatic cell DNA. Of these sequences, MADS-IX was found to be lost in the transition from primary to metastasis in two out of five ductal breast carcinoma cases. This sequence was localized on chromosome 10q21 by radiation hybrid mapping and fluorescence in situ hybridization. The PTEN gene, which is also located on chromosome 10q, was detected to be present by PCR in all five cases. On the contrary, a breast carcinoma cell line, HCC-1937, which has homozygous loss of a region encompassing the PTEN gene, showed the presence of MADS-IX. PCR screening of three additional breast carcinoma cell lines with known losses in specific chromosomal regions also showed the presence of MADS-IX. Conclusion These data suggest that MADS-IX possibly is part of a novel candidate metastasis-associated gene located close to the PTEN gene on chromosome 10q. The first set of PCR screening in five patient samples indicates that it could be used as a molecular marker for ductal mammary metastasis.

Inactivation of the protein product of the wild-type tumour suppressor gene p53 through complexing of the protein with the E6 oncoprotein of human papillomaviruses (HPV) in HPV-infected cells is thought to be important in the aetiology of cervical carcinoma. Mutations of p53 have also been reported in HPV-negative carcinomas, and we now demonstrate loss of heterozygosity (LOH) of chromosome region 17p13 (in which p53 is located) in such tumours. Immunocytochemical staining with monoclonal antimutant-p53 antibody revealed that the carcinomas with LOH on 17p and completely lacking HPV DNA sequences had mutant p53. Thus the LOH had apparently resulted in the loss of the wild-type allele. Consequently, in both HPV-positive and HPV-negative tumours there is loss of function of wild-type p53, in the former because the protein product of the p53 gene complexes with that of the viral E6 gene, in the latter because the protein is altered, presumably as a result of a direct alteration of the p53 gene but possibly because of other post-translational changes. That this mutant allele of the tumour suppressor gene may sometimes behave like an oncogene is suggested by the presence of more than the expected number of copies of the remaining chromosome 17 homologue in some carcinomas.

In the KOP translocation, t(X;14)(q13;q32), virtually the entire long arm of the X has been translocated to the end of the long arm of chromosome 14. Meiotic secondary nondisjunction in a female balanced carrier of the translocation has led to a son with two der(14) or 14-X chromosomes. The normal X chromosome is late replicating in the mother. One of the two 14-X chromosomes is late replicating in the son, with heavy terminal labeling of all but the centromeric end of the chromosome. This suggests that genetic inactivation has spread from the Xq segment of the translocation chromosome to at least two thirds of the segment derived from chromosome 14, and that the remaining proximal segment of chromosome 14 is possibly still genetically active. These findings provide an explanation for the phenotype: Klinefelter syndrome plus a few mild malformations that are sometimes seen in this syndrome but are also seen in duplication of the proximal portion of chromosome 14. Although the proband has a duplication of virtually an entire chromosome 14, 14(pter leads to q32), the phenotypic effect of the autosomal duplication has been mostly nullified by the spread of inactivation.

The sex distribution of 1421 induced abortuses and 2986 newborn infants was correlated with maternal contraceptive histories. Sex of abortuses was determined by chromosome and sex chromatin analyses. No statistically significant differences (P Greater Than 10) were found between the sex ratios either of the fetuses or of the infants of women who used hormonal (oral) contraceptives as compared to those of noncontraceptive controls nor between the induced and newborn series. Also, no correlation was found between sex of the conceptus and total duration of oral contraceptive use, or interval between termination of contraceptive use and conception. Therefore, if the use of low dose oral hormonal contraceptives has an effect on the sex of subsequent offspring, it is likely to be small since the 95% confidence interval for the sex ratios for the oral contraceptive groups divided by the sex ratios of the noncontraceptive group (odds ratio) are 0.80 to 1.22 for induced abortions, and 0.82 to 1.10 for newborns. These conclusions are not in agreement with some earlier reports, generally of small samples, but they are consistent with the results of Rothman and Liess (1976) from a sample of 6109 infants born to oral contraceptive users.The sex distribution of 1421 induced abortuses and 2986 newborn infants was correlated with maternal contraceptive histories. Sex of abortuses was determined by chromosome and sex chromatin analyses. No statistically significant differences were found between sex ratios either of the fetuses or of the infants of women who had used hormonal (oral) contraceptives as compared to those of noncontraceptive controls, nor between the induced and newborn series. Also, no correlation was found between sex of the conceptus and total duration of oral contraceptive use, or interval between termination of contraceptive use and conception. Therefore, if the use of low dose oral hormonal contraceptives has an effect on the sex of subsequent offspring, it is likely to be small since the 95% confidence interval for the sex ratios for the oral contraceptive groups divided by the sex ratios of the noncontraceptive group (odds ratio) are 0.80 to 1.22 for induced abortions, and 0.82 to 1.10 for newborns. These conclusions are not in agreement with some earlier reports, generally of small samples, but they are consistent with the results of Rothman and Liess (1976) from a sample of 6109 infants born to oral contraceptive users.

The deoxyribonucleic acid (DNA) content of Feulgen-stained interphase nuclei from human amnion epithelium and liver parenchyma as well as the DNA content of their sex chromatin or heterochromatic bodies was determined histophotometrically. In female nuclei the ratio between the nuclear DNA content and that of their sex chromatin or heterochromatic bodies remains constant irrespective of the polyploid state of the nucleus. Thus, in polyploid nuclei the heterochromatic bodies double their DNA content with each duplication of the diploid nuclear DNA content. Therefore, it is assumed that the large or multiple heterochromatic bodies of female polyploid nuclei are conjugated or multiple sex chromatin bodies. Some male diploid nuclei show a distinct heterochromatic body whose DNA content is about one-half that of a sex chromatin. About one-half of the polyploid male nuclei have heterochromatic bodies whose DNA content is approximately one-half of those of female nuclei of the corresponding polyploid class. This would indicate that in male diploid nuclei the single X chromosome sometimes leaves a heterochromatic rest one-half the size of a sex chromatin and in polyploid male nuclei the two or more X's may leave larger heterochromatic bodies. However, many male nuclei, even when polyploid, do not have distinct heterochromatic bodies. Possibly the heterochromatic portions of the X's have failed to join and form a sex chromatin-like body; or the Y inhibits the X from leaving a heterochromatic rest. The proposal of other authors that the sex chromatin is derived from but one of the X chromosomes of the female nucleus, the X in the male leaving no heterochromatic rest, is also considered. The DNA content does not vary significantly between nuclei with and without sex chromatin or heterochromatic bodies. It remains clear that female nuclei with abnormally large or multiple sex chromatin bodies and male nuclei with large distinct heterochromatic bodies are always polyploid.

The locations of the genes for fibronectin (FN) on chromosomes of human germ line and somatic cells were determined by in situ molecular hybridization with two 3H-labeled DNA probes, one for the region encoding the cell attachment domain of human FN, the other for the 3’ noncoding and part of the coding region. Pachytene chromosomes of two males and lymphocyte chromosomes of one of these males and a female were used. Two regions of hybridization on pachytene and somatic chromosome 2 (p14→p16 and q34→q36) were found, but not in all individuals. A third region of hybridization was found at 11q12.1→ql3.5 in meiotic, but not with significant frequency in somatic chromosomes. It is not clear if these differences between meiotic and somatic chromosomes, and the large differences between individuals at some of the other hybridization sites, resulted solely from technical factors. The differences between the findings in meiotic and somatic preparations might be due to the presence of four strands in pachytene chromosomes versus only one per somatic chromatid. Individual differences in DNA sequences in the chromosome segment containing the gene, differences in gene locations among individuals, or between meiotic and mitotic chromosomes might account for the other findings. The results confirm some of the earlier studies with cell hybrids that mapped FN genes to chromosomes 2 or 11. The combined findings suggest that some of these loci may be coding for the plasma form of FN and others for the cellular form. The expression of the different FN types by differentiated cells might then depend on the loci that are activated.

Two male diploid fibroblast strains, each carrying deficiency mutations at different X-linked loci (glucose-6-phosphate dehydrogenase and hypoxanthine-guanine-phosphoribosyltransferase) have been successfully hybridized. The resulting mononucleated hybrid cells have been shown to synthesize both normal gene products, indicating that both X chromosomes are functionally active in the hybrid cells. We believe this is the first reported example of intergenic complementation in fused human diploid cells.

Five patients are described with a partial deletion of the short arm of a chromosome No. 4, which was identified autoradiographically. The 4p- syndrome can be distinguished from the cri du chat (5p-) syndrome by the absence of a catlike cry and the presence of a lower birth weight, more marked psychomotor retardation, a flat beaked nose with a fish-shaped mouth, seizures, cleft palate, coloboma of the iris, preauricular or sacral dimple or sinus, hypospadias, midline scalp defect, underdeveloped dermal ridges on palm and sole, lower finger ridge count, and delayed bone maturation.

The earliest time at which ovulation may occur postpartum was investigated in this study of histological specimens of the endometrium. 128 endometrial biopsies were obtained, but only 92 had adequate material for study. Of the remaining 92 cases, decidual tissue was found in 11 cases, proliferative endometrium was found in 65 cases, and secretory endometrium was found in 16 cases. 12 of these 16 showed unequivocal secretory endometrium on or before the 43rd day postpartum; one was found as early as Day 33. The other 4 cases were found to be secretory between Days 44 and 93. 2 patients had menstruated once before biopsy. Those 16 cases with secretory endometrium ranged in age from 19-30 years; 12 of these women had had their pregnancy terminated between Weeks 38 and 41 and 3 women were terminated at Week 36, while 1 was terminated at Week of gestation. All women studied were nonlactating. Based on these data, contraceptive counseling postpartum should commence between Weeks 3 and 4 postpartum.