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Chromosome 6 Abnormalities in Ovarian Surface Epithelial Tumors of Borderline Malignancy Suggest a Genetic Continuum in the Progression Model of Ovarian Neoplasms¹

Laboratorio di Anatomia Patologica Ospedale di Circolo, Fondazione Macchi, 21100 Varese [M. G. T., C. F., C. R.]; and Dipartimento di Scienze Cliniche e Biologiche [B. B., D. F., P. B., R. Ce., C. C.], Clinica Ostetrica e Ginecologica [M. F.], and Dipartimento di Biologia Strutturale e Funzionale [R. Ci., R. T.], Universitèa dell’Insubria, 21100 Varese, Italy

Purpose: We used conventional cytogenetics, molecular cytogenetics, and molecular genetic analyses to study the pattern of allelic loss on chromosome 6q in a cohort of borderline epithelial ovarian tumors.

Experimental Design: Fifteen tumor samples were collected from patients undergoing surgery for ovarian tumors. The tumors of borderline malignancy, classified according to the standard criteria, included 4 mucinous and 11 serous tumors. Cytogenetic and molecular cytogenetic (with yeast artificial chromosome clones from 6q26-27) studies were performed on tumor areas contiguous to those used for histological examination ensuring the appropriate sampling. Moreover loss of heterozygosity analysis was performed using PCR amplification of eight microsatellite markers mapping on 6q27 (D6S193, D6S297), 6q26 (D6S305, D6S415, D6S441), 6q21 (D6S287), 6q16 (D6S311), and 6q14 (D6S300).

Results: Deletions of this chromosome arm, in particular of 6q24-27, were the most frequent lesions found in this set of tumors. In a tumor with a normal karyotype the only detectable alteration was a deletion of 300 kb within the D6S149–D6S193 interval at band 6q27. This is, to date, the smallest deletion described for borderline tumors.

Conclusion: Alterations in the above-mentioned interval are a common finding in advanced ovarian carcinomas but also in benign ovarian cysts, implying that some tumors of borderline malignancy may arise from benign tumors and that malignant ones may evolve from tumors of borderline malignancy. Genes located in 6q27 seem to be crucial for this mechanism of early events in ovarian tumorigenesis.

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