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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.

Die zellkerne in den Zellen der Septen und groszelligen Inseln der menschlichen Placenta enthalten in Praparaten, die von mannlichen Feten und Neugeborenen stammen, in 73% Sex-Chromatin. Die Septen und die groszelligen Inseln sind dadurch eindeutig als Bestandteile der Placenta materna gekennzeichnet. Fur die groszelligen Inseln sollte deshalb der alte richtige Name Deciduainseln verwendet werden.

IN previous reports from this laboratory it was noted that two or more sex chromatin bodies are present in some female nuclei, particularly in those from amnion epithelium1–3. Barr and Moore4 found multiple sex chromatin in some nuclei from malignant tumours and suggested that this is due to hyper-ploidy. Myers5 described multiple sex chromatin in teratomas. Atkin6 found that 7 out of 65 malignant tumours from females had two sex chromatin-like bodies per nucleus. He assumed that these nuclei were tetraploid and confirmed this with the aid of chromosome counts and estimations of deoxyribonucleic acid. It was of interest to determine if in non-pathological tissue the female nuclei in which we had found more than one sex chromatin body were of a polyploid nature and whether the occasional sex chromatin-like structure in male nuclei could be correlated with polyploidy.